Cell-cell fusion plays a critical role in the development of multicellular organisms, beginning with fertilization and continuing with formation of muscles, osteoclasts, and the placenta in mammals. Viral pathogens, including some members of poxvirus, paramyxovirus, herpesvirus, retrovirus, aquareovirus and orthoreovirus, cause infected cells to fuse with their neighbors, creating syncytia that contribute to disease pathology (Compton and Schwartz, 2017; Domachowske and Rosenberg, 1999; Moss, 2006; Smith et al., 2009). While the basic steps of membrane fusion have been extensively investigated in the context of enveloped virus entry and SNARE-mediated intracellular vesicle fusion (Südhof and Rothman, 2009), the molecules and pathways responsible for cell-cell fusion are less well understood. The best studied cell-cell fusogens are those with similarities to enveloped viral fusogens, including syncytin-1 (placental syncytiotrophoblasts formation) (Gong et al., 2005; Renard et al., 2005), Hap2 (conserved in eukaryotic gamete fusion) (Fédry et al., 2017; Feng et al., 2018; Liu et al., 2008b; Mori et al., 2006; Valansi et al., 2017; von Besser et al., 2006), and Eff-1/Aff-1 (C. elegans epithelial fusion) (Mohler et al., 2002; Pérez-Vargas et al., 2014; Sapir et al., 2008; Shemer et al., 2004; Zeev-Ben-Mordehai et al., 2014).

A key feature of viral and cell-cell fusogens is their tall ectodomains, which in their metastable pre-fusion state typically extend more than 10 nm from the membrane. Since the plasma membrane of cells is densely decorated with glycoproteins and glycolipids that could sterically block membranes from getting close enough to fuse, the tall ectodomains of viral and cell-cell fusogens may allow them to reach across the membrane gap and anchor to the apposing membrane, involving insertion of a fusion peptide for Class I viral fusogens or a fusion loop for Class II (Harrison, 2015; Podbilewicz, 2014). Once the fusogen links the two membranes, conformational changes cause the fusogen to fold back, pulling the two membranes into close contact and forming a stable post-fusion structure that promotes membrane fusion (Bullough et al., 1994; Chen et al., 1999; Harrison, 2015; Ivanovic and Harrison, 2015; Pancera et al., 2014; Podbilewicz, 2014; Sapir et al., 2008; Wilson et al., 1981). This conformational change, together with fusogen oligomerization and local cooperativity, is believed to be sufficient to provide the energy required to overcome the repulsive hydration barrier, which prevents membranes from coming closer than ~2 nm (Chernomordik and Kozlov, 2003; Harrison, 2015; Ivanovic and Harrison, 2015; Pérez-Vargas et al., 2014; Rand and Parsegian, 1989).

However, in other instances of cell-cell fusion, transmembrane proteins required for fusion are short by comparison and do not appear to undergo conformational changes, raising the question of how they bring two plasma membranes into close contact (Figure 1a). One example is the reptilian orthoreovirus fusion protein p14, a non-structural, single-pass transmembrane protein, that is expressed after viral entry. One of seven members of the FAST family of reovirus fusion proteins discovered by Duncan and colleagues (Ciechonska and Duncan, 2014; Corcoran and Duncan, 2004; Dawe and Duncan, 2002; Duncan et al., 1995; Duncan et al., 2004; Guo et al., 2013; Kim et al., 2015; Racine et al., 2009; Shmulevitz et al., 2004; Shmulevitz and Duncan, 2000; Wilcox and Compans, 1982), p14 has a membrane-disruptive ectodomain that is necessary to drive cell-cell fusion but extends only 0.7–1.5 nm from the plasma membrane (Corcoran et al., 2004; Corcoran et al., 2006). This short ectodomain has minimal secondary structure but is sufficient to disrupt opposing membranes either when added as a soluble fragment or when bare liposomes containing p14 are brought into close apposition through divalent cations (Corcoran et al., 2004; Top et al., 2005). However, cell surfaces are crowded with proteins that sterically block close apposition, and it is unclear how p14 overcomes the energetic barrier of cell surface protein crowding, as well as the ~2 nm repulsive hydration barrier, to drive cell-cell fusion (Chernomordik and Kozlov, 2003; Harrison, 2015; Rand and Parsegian, 1989). Yet, expression of p14 alone in cultured cells is sufficient to drive fusion with neighboring naïve cells (Corcoran and Duncan, 2004; Duncan et al., 2004).

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To address the question of how p14 promotes close contact between cells and drives membrane fusion, we studied cell-cell fusion in HEK293T cells transiently expressing p14. We found that p14 drives cell-cell fusion by hijacking the host cell actin cytoskeleton. Using a phosphorylation-dependent motif in its cytoplasmic domain, p14 triggers N-WASP-mediated assembly of branched actin, directly coupling actin assembly with a short membrane-disruptive ectodomain. This work suggests that energetic barriers to cell-cell fusion can be overcome by harnessing force generated from local actin assembly, and it points to an alternate means of promoting cell-cell fusion in processes where tall fusogens have not been identified.

Expression of p14 in HEK293T cells caused the cells to fuse with neighboring wild-type and p14-expressing cells, forming large multinucleated syncytia over the course of 24 hr (Figure 1b, Video 1), like previous reports for other cell types (Corcoran and Duncan, 2004). Partial cleavage of the p14 cytoplasmic tail, which also occurs during reptilian orthoreovirus infection (Top et al., 2009), liberates the C-terminus mCherry fluorescent tag from the transmembrane protein and serves as a convenient cytoplasmic marker of p14-expressing cells (Figure 1b, Figure 1—figure supplement 1a,b, and Video 2). At 12 hr post transfection, 5% of p14-expressing cells had 3 or more nuclei. At 24 hr post transfection, 34% of p14-expressing cells had 3 or nuclei (Figure 1c and d). In comparison, at 24 hr post transfection, no multinucleated cells were seen in cells transfected with mCherry alone (Figure 1—figure supplement 1c).

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To quantify cytoplasmic mixing during p14-mediated cell-cell fusion in a high-throughput manner, we expressed the two halves of splitYFP in two populations of HEK293T cells and mixed the cells together. When fusion between cells of the two populations occurred, the two halves of splitYFP self-associated in the mixed cytoplasm and fluoresced, allowing quantification by a plate reader (Figure 1e, and Figure 1—figure supplement 1d and e). Repeating the cell-cell fusion experiments above, the increase in YFP intensity in p14-expressing cells between 12 hr and 24 hr post transfection compared well with the increase in the percent of multinucleated cells, as quantified by counting nuclei (Figure 1f). Since YFP intensity is dependent on the percent of HEK293T cells expressing the two halves of splitYFP, the resultant YFP intensity was normalized to that of p14 WT and referred to as fusion index.

While the ectodomain of p14 is shorter than typical viral fusogens, its cytoplasmic domain is comparatively long (68 amino acids). To determine how the cytoplasmic domain of p14 might be involved in cell-cell fusion, we first truncated Q70-I125 (p14 Δcyto), retaining a polybasic motif needed for trafficking to the plasma membrane (Parmar et al., 2014). Although p14 Δcyto was properly trafficked to the plasma membrane (Figure 1—figure supplement 1f,g and h), cell-cell fusion was abrogated (Figure 1g, and Figure 1—figure supplement 1i). This is consistent with previous findings (Corcoran and Duncan, 2004), suggesting that p14 may be interacting with cellular components through its cytoplasmic tail to enable cell-cell fusion.

We next investigated whether post-translational modification of the cytoplasmic tail of p14 might play a role in cell-cell fusion. The p14 cytoplasmic tail is mostly disordered but has several tyrosines that could be phosphorylated (Figure 2a, and Figure 2—figure supplement 1a). To determine if these tyrosines are indeed phosphorylated, we immunoprecipitated p14 and probed with an anti-phosphotyrosine antibody, which confirmed p14 phosphorylation (Figure 2b). Next, we mutated each predicted tyrosine to phenylalanine (Y59F, Y77F, Y96F, Y100F, Y116F) and found that only one mutation (Y116F) decreased cell-cell fusion (Figure 2c and Figure 2—figure supplement 1b). We then used NetPhos3.1 and Scansite 4.0 to analyze the cytoplasmic tail of p14, and they predicted that Y116 is phosphorylated by c-src kinase (Figure 2d; Blom et al., 2004; Obenauer et al., 2003). To test this prediction, we mutated all other predicted phosphotyrosines of p14 to phenylalanine (YEY; Y59F, Y77F, Y96F, Y100F) and co-expressed it with constitutively active c-src mutant (CA c-src; Y527F). Y116 phosphorylation subsequently increased, indicating c-src phosphorylates p14 (Figure 2e). Consistent with this, Y116 phosphorylation was also increased when tyrosine phosphatases were broadly inhibited by addition of pervanadate (Figure 2e). Finally, to confirm that c-src is sufficient to phosphorylate Y116, we carried out a modified in vitro kinase assay using a peptide including Y116 (Y116-N121), along with CA c-src and kinase dead c-src (KD c-src; Y527F/K295R) mutants immunoprecipitated from HEK239T cells (Figure 2—figure supplement 1c and d). We found that CA c-src was sufficient to phosphorylate p14 cytoplasmic tail peptide, but KD c-src was not (Figure 2f), showing that c-src kinase is sufficient to phosphorylate Y116 in vitro. To verify this in live-cells, we expressed p14 WT in mouse embryonic fibroblasts lacking src, yes, and fyn kinase (SYF), as well as SYF cells supplemented with c-src (SYF + c-src). Despite lower transfection efficiency and reduced cell-cell fusion compared to HEK239T cells, SYF + c-src cells fused more than SYF cells (Figure 2g). Altogether, this demonstrates that c-src phosphorylates Y116 in the p14 cytoplasmic tail to drive cell-cell fusion.

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Excel Spreadsheet of counts for p14-expressing SYF and SYF+c-src cells for Figure 2g.

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To determine which cellular components could be interacting with p14 upon phosphorylation, we used the Eukaryotic Linear Motif (ELM) prediction tool to identify potential binding motifs (Dinkel et al., 2016). ELM predicted that phosphorylated Y116 binds to the SH2 domain of Grb2 as part of a Grb2 consensus-binding motif, YVNI (Figure 3a). To test this prediction, we carried out a co-immunoprecipitation assay and confirmed that p14 binds to Grb2 (Figure 3b). To determine if Grb2 binding is necessary for p14-mediated cell-cell fusion, we introduced two point mutations that disrupt the predicted Grb2 binding site both individually (Y116F, N118A) and together (FVAI; Y116F/N118A) (Figure 3b). While trafficking to the plasma membrane was intact, all three mutants severely attenuated cell-cell fusion (Figure 3c, Figure 3—figure supplement 1a,b and c), suggesting that Grb2 is important for p14-mediated fusion. To confirm that p14 is sufficient to recruit Grb2, we conjugated biotinylated p14 cytoplasmic tail peptide to streptavidin beads in vitro and incubated them with purified Grb2 fluorescently labeled with AF647 (Figure 3—figure supplement 1d). Consistent with our co-immunoprecipitation results, only phosphorylated Y116 bound to Grb2 (Figure 3d, and Figure 3—figure supplement 1e). When p14 Y116 phosphorylation is increased in cells with either co-expression of CA c-src or addition of the phosphatase inhibitor pervanadate, GFP-labeled Grb2 co-localized and enriched with p14 at the plasma membrane (Figure 3e and f). However, Grb2 did not co-localize or enrich with p14 at the plasma membrane when the Grb2 binding site was mutated to FVAI and co-expressed with CA src or treated with pervanadate (Figure 3e and f, and Figure 3—figure supplement 1f and g).

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Excel Spreadsheet of plasma membrane enrichment of Grb2-GFP in cells expressing CA-src alone or with p14-WT-mcherry or with p14-FVAI mcherry.

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Having shown that Grb2 binds to the p14 cytoplasmic tail in a phosphorylation-dependent manner, we next sought to determine mechanistically how Grb2, an adaptor protein with two SH3 domains, plays a role in p14-mediated cell-cell fusion. The N-terminal SH3 domain of Grb2 binds to SOS, activating Ras, which in turn activates Raf kinase and the MAPK-ERK1/2 pathway, while the C-terminal SH3 domain of Grb2 binds to the actin nucleation promoting factor N-WASP, which binds to Arp2/3 and nucleates branched actin assembly (Figure 4a). To determine if one or both pathways are important for fusion, we first treated cells expressing p14 with sorafenib tosylate, an inhibitor of Raf kinase, but found no effect on cell-cell fusion at up to 100 times the IC₅₀ (Figure 4b). We next considered whether branched actin networks could be directly involved in p14-mediated cell-cell fusion. Building on previous work showing that cytochalasin D disrupts fusion of p14-expressing cells (Salsman et al., 2008), we treated p14-expressing cells with wiskostatin, an inhibitor of N-WASP. We found that p14 trafficking to the plasma membrane fusion was unperturbed, but cell-cell fusion was significantly reduced (Figure 4b, Figure 4—figure supplement 1a and b). We then treated p14-expressing cells with CK-666 to inhibit the Arp2/3 complex, which nucleates branched actin filaments, and found that fusion was reduced in a dose-dependent manner despite proper trafficking of p14 to the plasma membrane (Figure 4b, Figure 4—figure supplement 1a and b). Interestingly, treating p14-expressing cells with smifH2, an inhibitor of formins, enhanced cell-cell fusion (Figure 4b), perhaps due to increased branched actin assembly that has been observed when formins are broadly inhibited (Burke et al., 2014).

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Excel Spreadsheet of counts and distribution for p14-expressing HEK293T cells over-expressing Grb2 mutants for Figure 4c.

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Excel Spreadsheet of counts and distribution for p14-expressing N-WASP -/- or +/+ mouse embryonic fibroblasts for Figure 4d.

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To test whether the reduction in cell-cell fusion with wiskostatin and CK-666 was the result of a direct link between N-WASP and p14 or a more general inhibition of actin activity, we over-expressed Grb2 mutants that can only bind to either SOS or N-WASP by truncating either the N- or C-terminal SH3 domains, respectively. We found that both of these Grb2 mutants bound to p14 WT and co-localized with phosphorylated p14 in pervanadate-treated live cell images (Figure 4—figure supplement 1c), confirming that the mutations did not disrupt interactions with p14. However, when the Grb2 N-terminal mutant that can bind only to SOS (Nterm) was over-expressed, the extent of p14-mediated cell-cell fusion was reduced, similar to when endogenous Grb2 binding was reduced by overexpression of the Grb2 SH2 domain (Figure 4c, Figure 4—figure supplement 1d,e and f). When a Grb2 C-terminal mutant that can bind only to N-WASP (Cterm) was over-expressed, p14-mediated cell-cell fusion was restored to a level comparable to that of endogenous Grb2 in WT cells (Figure 4c, Figure 4—figure supplement 1d,e and f). To further confirm the specificity of N-WASP-nucleated branched actin assembly in p14-mediated cell-cell fusion, we expressed p14 WT in N-WASP null (N-WASP -/-) mouse embryonic fibroblasts. We found that the extent of p14-mediated cell-cell fusion was attenuated in N-WASP -/- cells compared to wild-type mouse embryonic fibroblasts (Figure 4d, Figure 4—figure supplement 1g).

To determine whether N-WASP binding to Grb2 and the p14 cytoplasmic tail is sufficient to nucleate actin assembly, we used an in vitro actin-based motility assay. We bound biotinylated p14 cytoplasmic tail peptides to streptavidin beads in a purified actin motility mixture containing N-WASP (lacking the EVH1 domain), Arp2/3, profilin, cofilin, capping protein and actin, supplemented with Grb2 (Figure 4—figure supplement 1h). When Y116 of the p14 cytoplasmic tail peptide was phosphorylated, actin tails were nucleated from the bead (Figure 4e), but when Y116 was not phosphorylated, actin tails were not observed (Figure 4e). This confirms that Grb2 is necessary and sufficient to recruit N-WASP to the p14 cytoplasmic tail and can nucleate localized branched actin networks when p14 is present.

We next investigated whether branched actin network assembly must be directly coupled to the fusogenic ectodomain, or whether the fusogenic ectodomain can simply be present in the same membrane as actin assembly by the cytoplasmic tail of p14. To test the necessity for direct coupling, we co-expressed the ectodomain deletion mutant (Δecto; ΔM1-T35), which traffics to the plasma membrane and binds Grb2 (Figure 5—figure supplement 1a and b) and the cytoplasmic tail deletion mutant (Δcyto) in the same cell. Interestingly, we found that cell-cell fusion was abolished (Figure 5a, and Figure 5—figure supplement 1c), despite the presence of both halves of p14. This indicates that actin assembly localized to the p14 ectodomain is necessary to drive fusion. This also suggests why native Arp2/3-generated branched actin networks at cell-cell contacts (Efimova and Svitkina, 2018) are not sufficient to cause spontaneous cell-cell fusion. We note that the mechanism described here is in addition to the role of the actin cytoskeleton at E-cadherin-mediated cell-cell adhesion sites (Salsman et al., 2008).

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Excel Spreadsheet of counts and distribution for p14-expressing HEK293T cells over-expressing R47 constructs for Figure 5c.

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If actin assembly directly coupled to p14 is necessary and sufficient for the fusogenic activity of p14, then it should be possible to drive cell-cell fusion by creating an alternate link between p14 and branched actin network assembly. To test this idea, we engineered a fusion protein that binds to p14 consisting of Grb2 SH2 domain and a 47-residue peptide from EspF_U of enterohemorrhagic E. coli (EHEC) (Figure 5b). This 47-residue peptide binds to and relieves the auto-inhibition of endogenous N-WASP, nucleating branched actin network (Cheng et al., 2008; Sallee et al., 2008). Fusion of this peptide with the Grb2 SH2 domain, which we confirmed binds to phosphorylated p14 (Figure 5—figure supplement 1d), enables binding to WT p14. When we expressed this fusion protein (SH2-R47) together with p14 in HEK293T, cell-cell fusion was significantly higher than when the SH2 domain lacking R47 was expressed to a similar level (Figure 5c, Figure 5—figure supplement 1e,f and g). This result demonstrates that direct coupling of branched actin assembly to p14 is necessary and sufficient for fusion.

This study reveals how a viral pathogen hijacks branched actin network assembly to drive cell-cell fusion, reminiscent of how the pathogens Listeria monocytogenes and vaccinia virus hijack branched actin network assembly to move within and between cells (Welch and Way, 2013). Here we show that the reptilian orthoreovirus fusogen p14 accomplishes this by presenting a c-src kinase substrate in its cytoplasmic tail, binding the host cell adaptor protein Grb2, and initiating branched actin assembly through the host nucleation promoting factor N-WASP. Since p14 ectodomain extends only 0.7–1.5 nm from the plasma membrane (Corcoran et al., 2006), it cannot interact with apposing membrane through the ~2 nm repulsive hydration barrier. If that barrier can be overcome, for example by using divalent cations to bring bare membranes containing negatively charged PS together in vitro, the p14 ectodomain is able to disrupt and mix membranes (Top et al., 2005). However, it is unclear how such close membrane-membrane interaction is achieved on the crowded plasma membrane where the lipid bilayer is sterically blocked by dense membrane proteins.

We propose that the primary role of branched actin network assembly by p14 is to physically push the fusogenic ectodomain into the opposing plasma membrane, a step normally carried out by conformational changes of tall fusogens. In this model, localized force generation by branched actin network assembly around p14’s cytoplasmic domain drives close membrane apposition by coupling to and pushing against the cortical actin cytoskeleton, much like other actin-based membrane protrusions. This close apposition in the presence of p14’s membrane-disruptive ectodomain, which contains hydrophobic residues and myristoylation that are known to be necessary for fusion (Corcoran et al., 2004; Corcoran and Duncan, 2004; Top et al., 2009), may be sufficient to drive cell-cell fusion. Several other roles of the actin cytoskeleton may also be important for p14-bsaed cell-cell fusion. The actin cytoskeleton could promote clustering of p14 ectodomains into sub-diffraction-limited domains (Köster and Mayor, 2016), although enrichment of p14 or phosphorylated p14 was not readily observed at sites of fusion (Figure 5—figure supplement 2a,b,c and d). The actin cytoskeleton could also change local membrane curvature and tension (Kozlov and Chernomordik, 2015), block fusion pore closure, and/or actively expand the fusion pore (Kozlov and Chernomordik, 2015), all of which would promote cell-cell fusion by p14.

Membrane fusion driven by other fusogens has long implicated the actin cytoskeleton (Kondo et al., 2015; Sanderson et al., 1998). The proposed roles of the actin cytoskeleton include regulating the activity, localization and enrichment of fusogens at fusion sites (Yang et al., 2017), regulating protein-protein interactions (Wakimoto et al., 2013), and enlarging the fusion pore (Wurth et al., 2010; Zheng and Chang, 1990). In cases where the putative fusogen remains unidentified or the mechanism of fusion remains unclear, the actin cytoskeleton has been suggested as a key player. Examples include formation of signaling scaffolds and protrusive structures during osteoclast fusion (Oikawa et al., 2012), macrophage fusion (Faust et al., 2019), and myoblast fusion in Drosophila (Kim et al., 2015; Sens et al., 2010). Protrusive membrane structures generated by branched actin assembly have also been observed at fusogenic synapses (Shilagardi et al., 2013) and can be formed in vitro (Liu et al., 2008a; Simon et al., 2019).

Our findings may be relevant to putative fusogens like myomixer, a short extracellular peptide that is required for myoblast fusion (Bi et al., 2018; Leikina et al., 2018; Millay et al., 2013; Quinn et al., 2017; Sampath et al., 2018; Zhang et al., 2017) and does not resemble conformational-change based fusogens. Like p14, myomixer, together with its partner myomaker, could harness the actin cytoskeleton to drive cell-cell fusion by physically forcing a short fusogenic ectodomain through dense cell surface proteins and into contact with an apposing membrane. In this model of cell-cell fusion, local forces generated by the cytoskeleton, rather than by conformational changes in a tall fusogen, provide a powerful tool for cells and pathogens to create multinucleated structures.

All data generated or analysed during this study are included in the manuscript and supporting files.

1. 1. Bi P
   2. McAnally JR
   3. Shelton JM
   4. Sánchez-Ortiz E
   5. Bassel-Duby R
   6. Olson EN

   (2018) Fusogenic micropeptide myomixer is essential for satellite cell fusion and muscle regeneration

   PNAS 115:3864–3869.

   https://doi.org/10.1073/pnas.1800052115

   • PubMed
   • Google Scholar
2. 1. Bieling P
   2. Li TD
   3. Weichsel J
   4. McGorty R
   5. Jreij P
   6. Huang B
   7. Fletcher DA
   8. Mullins RD

   (2016) Force feedback controls motor activity and mechanical properties of Self-Assembling branched actin networks

   Cell 164:115–127.

   https://doi.org/10.1016/j.cell.2015.11.057

   • PubMed
   • Google Scholar
3. 1. Blom N
   2. Sicheritz-Pontén T
   3. Gupta R
   4. Gammeltoft S
   5. Brunak S

   (2004) Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence

   Proteomics 4:1633–1649.

   https://doi.org/10.1002/pmic.200300771

   • PubMed
   • Google Scholar
4. 1. Bullough PA
   2. Hughson FM
   3. Skehel JJ
   4. Wiley DC

   (1994) Structure of influenza haemagglutinin at the pH of membrane fusion

   Nature 371:37–43.

   https://doi.org/10.1038/371037a0

   • PubMed
   • Google Scholar
5. 1. Burke TA
   2. Christensen JR
   3. Barone E
   4. Suarez C
   5. Sirotkin V
   6. Kovar DR

   (2014) Homeostatic actin cytoskeleton networks are regulated by assembly factor competition for monomers

   Current Biology 24:579–585.

   https://doi.org/10.1016/j.cub.2014.01.072

   • PubMed
   • Google Scholar
6. 1. Chen J
   2. Skehel JJ
   3. Wiley DC

   (1999) N- and C-terminal residues combine in the fusion-pH influenza hemagglutinin HA(2) subunit to form an N cap that terminates the triple-stranded coiled coil

   PNAS 96:8967–8972.

   https://doi.org/10.1073/pnas.96.16.8967

   • PubMed
   • Google Scholar
7. 1. Cheng HC
   2. Skehan BM
   3. Campellone KG
   4. Leong JM
   5. Rosen MK

   (2008) Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U)

   Nature 454:1009–1013.

   https://doi.org/10.1038/nature07160

   • PubMed
   • Google Scholar
8. 1. Chernomordik LV
   2. Kozlov MM

   (2003) Protein-lipid interplay in fusion and fission of biological membranes

   Annual Review of Biochemistry 72:175–207.

   https://doi.org/10.1146/annurev.biochem.72.121801.161504

   • PubMed
   • Google Scholar
9. 1. Ciechonska M
   2. Duncan R

   (2014) Reovirus FAST proteins: virus-encoded cellular fusogens

   Trends in Microbiology 22:715–724.

   https://doi.org/10.1016/j.tim.2014.08.005

   • PubMed
   • Google Scholar
10. 1. Compton AA
    2. Schwartz O

    (2017) They might be giants: does syncytium formation sink or spread HIV infection?

    PLOS Pathogens 13:e1006099.

    https://doi.org/10.1371/journal.ppat.1006099

    • PubMed
    • Google Scholar
11. 1. Corcoran JA
    2. Syvitski R
    3. Top D
    4. Epand RM
    5. Epand RF
    6. Jakeman D
    7. Duncan R

    (2004) Myristoylation, a protruding loop, and structural plasticity are essential features of a nonenveloped virus fusion peptide motif

    Journal of Biological Chemistry 279:51386–51394.

    https://doi.org/10.1074/jbc.M406990200

    • PubMed
    • Google Scholar
12. 1. Corcoran JA
    2. Salsman J
    3. de Antueno R
    4. Touhami A
    5. Jericho MH
    6. Clancy EK
    7. Duncan R

    (2006) The p14 fusion-associated small transmembrane (FAST) protein effects membrane fusion from a subset of membrane microdomains

    Journal of Biological Chemistry 281:31778–31789.

    https://doi.org/10.1074/jbc.M602566200

    • PubMed
    • Google Scholar
13. 1. Corcoran JA
    2. Duncan R

    (2004) Reptilian reovirus utilizes a small type III protein with an external myristylated amino terminus to mediate cell-cell fusion

    Journal of Virology 78:4342–4351.

    https://doi.org/10.1128/JVI.78.8.4342-4351.2004

    • PubMed
    • Google Scholar
14. 1. Dagliyan O
    2. Tarnawski M
    3. Chu PH
    4. Shirvanyants D
    5. Schlichting I
    6. Dokholyan NV
    7. Hahn KM

    (2016) Engineering extrinsic disorder to control protein activity in living cells

    Science 354:1441–1444.

    https://doi.org/10.1126/science.aah3404

    • PubMed
    • Google Scholar
15. 1. Dawe S
    2. Duncan R

    (2002) The S4 genome segment of baboon reovirus is bicistronic and encodes a novel fusion-associated small transmembrane protein

    Journal of Virology 76:2131–2140.

    https://doi.org/10.1128/jvi.76.5.2131-2140.2002

    • PubMed
    • Google Scholar
16. 1. Dinkel H
    2. Van Roey K
    3. Michael S
    4. Kumar M
    5. Uyar B
    6. Altenberg B
    7. Milchevskaya V
    8. Schneider M
    9. Kühn H
    10. Behrendt A
    11. Dahl SL
    12. Damerell V
    13. Diebel S
    14. Kalman S
    15. Klein S
    16. Knudsen AC
    17. Mäder C
    18. Merrill S
    19. Staudt A
    20. Thiel V
    21. Welti L
    22. Davey NE
    23. Diella F
    24. Gibson TJ

    (2016) ELM 2016--data update and new functionality of the eukaryotic linear motif resource

    Nucleic Acids Research 44:D294–D300.

    https://doi.org/10.1093/nar/gkv1291

    • PubMed
    • Google Scholar
17. 1. Domachowske JB
    2. Rosenberg HF

    (1999) Respiratory syncytial virus infection: immune response, immunopathogenesis, and treatment

    Clinical Microbiology Reviews 12:298–309.

    https://doi.org/10.1128/CMR.12.2.298

    • PubMed
    • Google Scholar
18. 1. Duncan R
    2. Murphy FA
    3. Mirkovic RR

    (1995) Characterization of a novel syncytium-inducing baboon reovirus

    Virology 212:752–756.

    https://doi.org/10.1006/viro.1995.1536

    • PubMed
    • Google Scholar
19. 1. Duncan R
    2. Corcoran J
    3. Shou J
    4. Stoltz D

    (2004) Reptilian reovirus: a new fusogenic Orthoreovirus species

    Virology 319:131–140.

    https://doi.org/10.1016/j.virol.2003.10.025

    • PubMed
    • Google Scholar
20. 1. Efimova N
    2. Svitkina TM

    (2018) Branched actin networks push against each other at Adherens junctions to maintain cell-cell adhesion

    Journal of Cell Biology 217:1827–1845.

    https://doi.org/10.1083/jcb.201708103

    • PubMed
    • Google Scholar
21. 1. Faust JJ
    2. Balabiyev A
    3. Heddleston JM
    4. Podolnikova NP
    5. Baluch DP
    6. Chew TL
    7. Ugarova TP

    (2019) An actin-based protrusion originating from a podosome-enriched region initiates macrophage fusion

    Molecular Biology of the Cell 30:2254–2267.

    https://doi.org/10.1091/mbc.E19-01-0009

    • PubMed
    • Google Scholar
22. 1. Fédry J
    2. Liu Y
    3. Péhau-Arnaudet G
    4. Pei J
    5. Li W
    6. Tortorici MA
    7. Traincard F
    8. Meola A
    9. Bricogne G
    10. Grishin NV
    11. Snell WJ
    12. Rey FA
    13. Krey T

    (2017) The ancient gamete fusogen HAP2 is a eukaryotic class II fusion protein

    Cell 168:904–915.

    https://doi.org/10.1016/j.cell.2017.01.024

    • PubMed
    • Google Scholar
23. 1. Feng J
    2. Dong X
    3. Pinello J
    4. Zhang J
    5. Lu C
    6. Iacob RE
    7. Engen JR
    8. Snell WJ
    9. Springer TA

    (2018) Fusion surface structure, function, and dynamics of gamete fusogen HAP2

    eLife 7:e39772.

    https://doi.org/10.7554/eLife.39772

    • PubMed
    • Google Scholar
24. 1. Gong R
    2. Peng X
    3. Kang S
    4. Feng H
    5. Huang J
    6. Zhang W
    7. Lin D
    8. Tien P
    9. Xiao G

    (2005) Structural characterization of the fusion core in Syncytin, envelope protein of human endogenous retrovirus family W

    Biochemical and Biophysical Research Communications 331:1193–1200.

    https://doi.org/10.1016/j.bbrc.2005.04.032

    • PubMed
    • Google Scholar
25. 1. Guo H
    2. Sun X
    3. Yan L
    4. Shao L
    5. Fang Q

    (2013) The NS16 protein of aquareovirus-C is a fusion-associated small transmembrane (FAST) protein, and its activity can be enhanced by the nonstructural protein NS26

    Virus Research 171:129–137.

    https://doi.org/10.1016/j.virusres.2012.11.011

    • PubMed
    • Google Scholar
26. 1. Harris AR
    2. Belardi B
    3. Jreij P
    4. Wei K
    5. Shams H
    6. Bausch A
    7. Fletcher DA

    (2019) Steric regulation of tandem calponin homology domain actin-binding affinity

    Molecular Biology of the Cell 30:3112–3122.

    https://doi.org/10.1091/mbc.E19-06-0317

    • PubMed
    • Google Scholar
27. 1. Harrison SC

    (2015) Viral membrane fusion

    Virology 479-480:498–507.

    https://doi.org/10.1016/j.virol.2015.03.043

    • PubMed
    • Google Scholar
28. 1. Ivanovic T
    2. Harrison SC

    (2015) Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion

    eLife 4:e11009.

    https://doi.org/10.7554/eLife.11009

    • PubMed
    • Google Scholar
29. 1. Kim JH
    2. Ren Y
    3. Ng WP
    4. Li S
    5. Son S
    6. Kee YS
    7. Zhang S
    8. Zhang G
    9. Fletcher DA
    10. Robinson DN
    11. Chen EH

    (2015) Mechanical tension drives cell membrane fusion

    Developmental Cell 32:561–573.

    https://doi.org/10.1016/j.devcel.2015.01.005

    • PubMed
    • Google Scholar
30. 1. Kondo N
    2. Marin M
    3. Kim JH
    4. Desai TM
    5. Melikyan GB

    (2015) Distinct requirements for HIV-cell fusion and HIV-mediated cell-cell fusion

    Journal of Biological Chemistry 290:6558–6573.

    https://doi.org/10.1074/jbc.M114.623181

    • PubMed
    • Google Scholar
31. 1. Köster DV
    2. Mayor S

    (2016) Cortical actin and the plasma membrane: inextricably intertwined

    Current Opinion in Cell Biology 38:81–89.

    https://doi.org/10.1016/j.ceb.2016.02.021

    • PubMed
    • Google Scholar
32. 1. Kozlov MM
    2. Chernomordik LV

    (2015) Membrane tension and membrane fusion

    Current Opinion in Structural Biology 33:61–67.

    https://doi.org/10.1016/j.sbi.2015.07.010

    • PubMed
    • Google Scholar
33. 1. Leikina E
    2. Gamage DG
    3. Prasad V
    4. Goykhberg J
    5. Crowe M
    6. Diao J
    7. Kozlov MM
    8. Chernomordik LV
    9. Millay DP

    (2018) Myomaker and myomerger work independently to control distinct steps of membrane remodeling during myoblast fusion

    Developmental Cell 46:767–780.

    https://doi.org/10.1016/j.devcel.2018.08.006

    • PubMed
    • Google Scholar
34. 1. Liu AP
    2. Richmond DL
    3. Maibaum L
    4. Pronk S
    5. Geissler PL
    6. Fletcher DA

    (2008a) Membrane-induced bundling of actin filaments

    Nature Physics 4:789–793.

    https://doi.org/10.1038/nphys1071

    • PubMed
    • Google Scholar
35. 1. Liu Y
    2. Tewari R
    3. Ning J
    4. Blagborough AM
    5. Garbom S
    6. Pei J
    7. Grishin NV
    8. Steele RE
    9. Sinden RE
    10. Snell WJ
    11. Billker O

    (2008b) The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and plasmodium gametes

    Genes & Development 22:1051–1068.

    https://doi.org/10.1101/gad.1656508

    • PubMed
    • Google Scholar
36. 1. Millay DP
    2. O'Rourke JR
    3. Sutherland LB
    4. Bezprozvannaya S
    5. Shelton JM
    6. Bassel-Duby R
    7. Olson EN

    (2013) Myomaker is a membrane activator of myoblast fusion and muscle formation

    Nature 499:301–305.

    https://doi.org/10.1038/nature12343

    • PubMed
    • Google Scholar
37. 1. Mohler WA
    2. Shemer G
    3. del Campo JJ
    4. Valansi C
    5. Opoku-Serebuoh E
    6. Scranton V
    7. Assaf N
    8. White JG
    9. Podbilewicz B

    (2002) The type I membrane protein EFF-1 is essential for developmental cell fusion

    Developmental Cell 2:355–362.

    https://doi.org/10.1016/S1534-5807(02)00129-6

    • PubMed
    • Google Scholar
38. 1. Mori T
    2. Kuroiwa H
    3. Higashiyama T
    4. Kuroiwa T

    (2006) GENERATIVE CELL SPECIFIC 1 is essential for angiosperm fertilization

    Nature Cell Biology 8:64–71.

    https://doi.org/10.1038/ncb1345

    • PubMed
    • Google Scholar
39. 1. Moss B

    (2006) Poxvirus entry and membrane fusion

    Virology 344:48–54.

    https://doi.org/10.1016/j.virol.2005.09.037

    • PubMed
    • Google Scholar
40. 1. Obenauer JC
    2. Cantley LC
    3. Yaffe MB

    (2003) Scansite 2.0: proteome-wide prediction of cell signaling interactions using short sequence motifs

    Nucleic Acids Research 31:3635–3641.

    https://doi.org/10.1093/nar/gkg584

    • PubMed
    • Google Scholar
41. 1. Oikawa T
    2. Oyama M
    3. Kozuka-Hata H
    4. Uehara S
    5. Udagawa N
    6. Saya H
    7. Matsuo K

    (2012) Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion

    The Journal of Cell Biology 197:553–568.

    https://doi.org/10.1083/jcb.201111116

    • PubMed
    • Google Scholar
42. 1. Okrut J
    2. Prakash S
    3. Wu Q
    4. Kelly MJ
    5. Taunton J

    (2015) Allosteric N-WASP activation by an inter-SH3 domain Linker in nck

    PNAS 112:E6436–E6445.

    https://doi.org/10.1073/pnas.1510876112

    • PubMed
    • Google Scholar
43. 1. Pancera M
    2. Zhou T
    3. Druz A
    4. Georgiev IS
    5. Soto C
    6. Gorman J
    7. Huang J
    8. Acharya P
    9. Chuang GY
    10. Ofek G
    11. Stewart-Jones GB
    12. Stuckey J
    13. Bailer RT
    14. Joyce MG
    15. Louder MK
    16. Tumba N
    17. Yang Y
    18. Zhang B
    19. Cohen MS
    20. Haynes BF
    21. Mascola JR
    22. Morris L
    23. Munro JB
    24. Blanchard SC
    25. Mothes W
    26. Connors M
    27. Kwong PD

    (2014) Structure and immune recognition of trimeric pre-fusion HIV-1 env

    Nature 514:455–461.

    https://doi.org/10.1038/nature13808

    • PubMed
    • Google Scholar
44. 1. Parmar HB
    2. Barry C
    3. Duncan R

    (2014) Polybasic trafficking signal mediates golgi export, ER retention or ER export and retrieval based on membrane-proximity

    PLOS ONE 9:e94194.

    https://doi.org/10.1371/journal.pone.0094194

    • PubMed
    • Google Scholar
45. 1. Pérez-Vargas J
    2. Krey T
    3. Valansi C
    4. Avinoam O
    5. Haouz A
    6. Jamin M
    7. Raveh-Barak H
    8. Podbilewicz B
    9. Rey FA

    (2014) Structural basis of eukaryotic cell-cell fusion

    Cell 157:407–419.

    https://doi.org/10.1016/j.cell.2014.02.020

    • PubMed
    • Google Scholar
46. 1. Podbilewicz B

    (2014) Virus and cell fusion mechanisms

    Annual Review of Cell and Developmental Biology 30:111–139.

    https://doi.org/10.1146/annurev-cellbio-101512-122422

    • PubMed
    • Google Scholar
47. 1. Quinn ME
    2. Goh Q
    3. Kurosaka M
    4. Gamage DG
    5. Petrany MJ
    6. Prasad V
    7. Millay DP

    (2017) Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development

    Nature Communications 8:15665.

    https://doi.org/10.1038/ncomms15665

    • PubMed
    • Google Scholar
48. 1. Racine T
    2. Hurst T
    3. Barry C
    4. Shou J
    5. Kibenge F
    6. Duncan R

    (2009) Aquareovirus effects syncytiogenesis by using a novel member of the FAST protein family translated from a noncanonical translation start site

    Journal of Virology 83:5951–5955.

    https://doi.org/10.1128/JVI.00171-09

    • PubMed
    • Google Scholar
49. 1. Rand RP
    2. Parsegian VA

    (1989) Hydration forces between phospholipid bilayers

    Biochimica Et Biophysica Acta (BBA) - Reviews on Biomembranes 988:351–376.

    https://doi.org/10.1016/0304-4157(89)90010-5

    • Google Scholar
50. 1. Renard M
    2. Varela PF
    3. Letzelter C
    4. Duquerroy S
    5. Rey FA
    6. Heidmann T

    (2005) Crystal structure of a pivotal domain of human syncytin-2, a 40 million years old endogenous retrovirus fusogenic envelope gene captured by primates

    Journal of Molecular Biology 352:1029–1034.

    https://doi.org/10.1016/j.jmb.2005.07.058

    • PubMed
    • Google Scholar
51. 1. Sallee NA
    2. Rivera GM
    3. Dueber JE
    4. Vasilescu D
    5. Mullins RD
    6. Mayer BJ
    7. Lim WA

    (2008) The pathogen protein EspF(U) hijacks actin polymerization using mimicry and multivalency

    Nature 454:1005–1008.

    https://doi.org/10.1038/nature07170

    • PubMed
    • Google Scholar
52. 1. Salsman J
    2. Top D
    3. Barry C
    4. Duncan R

    (2008) A virus-encoded cell-cell fusion machine dependent on surrogate adhesins

    PLOS Pathogens 4:e1000016.

    https://doi.org/10.1371/journal.ppat.1000016

    • PubMed
    • Google Scholar
53. 1. Sampath SC
    2. Sampath SC
    3. Millay DP

    (2018) Myoblast fusion confusion: the resolution begins

    Skeletal Muscle 8:3.

    https://doi.org/10.1186/s13395-017-0149-3

    • PubMed
    • Google Scholar
54. 1. Sanderson CM
    2. Frischknecht F
    3. Way M
    4. Hollinshead M
    5. Smith GL

    (1998) Roles of vaccinia virus EEV-specific proteins in intracellular actin tail formation and low pH-induced cell-cell fusion

    Journal of General Virology 79:1415–1425.

    https://doi.org/10.1099/0022-1317-79-6-1415

    • PubMed
    • Google Scholar
55. 1. Sapir A
    2. Avinoam O
    3. Podbilewicz B
    4. Chernomordik LV

    (2008) Viral and developmental cell fusion mechanisms: conservation and divergence

    Developmental Cell 14:11–21.

    https://doi.org/10.1016/j.devcel.2007.12.008

    • PubMed
    • Google Scholar
56. 1. Sens KL
    2. Zhang S
    3. Jin P
    4. Duan R
    5. Zhang G
    6. Luo F
    7. Parachini L
    8. Chen EH

    (2010) An invasive podosome-like structure promotes fusion pore formation during myoblast fusion

    The Journal of Cell Biology 191:1013–1027.

    https://doi.org/10.1083/jcb.201006006

    • PubMed
    • Google Scholar
57. 1. Shemer G
    2. Suissa M
    3. Kolotuev I
    4. Nguyen KC
    5. Hall DH
    6. Podbilewicz B

    (2004) EFF-1 is sufficient to initiate and execute tissue-specific cell fusion in C. elegans

    Current Biology 14:1587–1591.

    https://doi.org/10.1016/j.cub.2004.07.059

    • PubMed
    • Google Scholar
58. 1. Shilagardi K
    2. Li S
    3. Luo F
    4. Marikar F
    5. Duan R
    6. Jin P
    7. Kim JH
    8. Murnen K
    9. Chen EH

    (2013) Actin-propelled invasive membrane protrusions promote fusogenic protein engagement during cell-cell fusion

    Science 340:359–363.

    https://doi.org/10.1126/science.1234781

    • PubMed
    • Google Scholar
59. 1. Shmulevitz M
    2. Epand RF
    3. Epand RM
    4. Duncan R

    (2004) Structural and functional properties of an unusual internal fusion peptide in a nonenveloped virus membrane fusion protein

    Journal of Virology 78:2808–2818.

    https://doi.org/10.1128/JVI.78.6.2808-2818.2004

    • PubMed
    • Google Scholar
60. 1. Shmulevitz M
    2. Duncan R

    (2000) A new class of fusion-associated small transmembrane (FAST) proteins encoded by the non-enveloped fusogenic Reoviruses

    The EMBO Journal 19:902–912.

    https://doi.org/10.1093/emboj/19.5.902

    • PubMed
    • Google Scholar
61. 1. Simon C
    2. Kusters R
    3. Caorsi V
    4. Allard A
    5. Abou-Ghali M
    6. Manzi J
    7. Di Cicco A
    8. Lévy D
    9. Lenz M
    10. Joanny J-F
    11. Campillo C
    12. Plastino J
    13. Sens P
    14. Sykes C

    (2019) Actin dynamics drive cell-like membrane deformation

    Nature Physics 15:602–609.

    https://doi.org/10.1038/s41567-019-0464-1

    • Google Scholar
62. 1. Smith EC
    2. Popa A
    3. Chang A
    4. Masante C
    5. Dutch RE

    (2009) Viral entry mechanisms: the increasing diversity of paramyxovirus entry

    FEBS Journal 276:7217–7227.

    https://doi.org/10.1111/j.1742-4658.2009.07401.x

    • PubMed
    • Google Scholar
63. 1. Spudich JA
    2. Watt S

    (1971)

    The regulation of rabbit skeletal muscle contraction. I. biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin

    The Journal of Biological Chemistry 246:4866–4871.

    • PubMed
    • Google Scholar
64. 1. Su X
    2. Ditlev JA
    3. Hui E
    4. Xing W
    5. Banjade S
    6. Okrut J
    7. King DS
    8. Taunton J
    9. Rosen MK
    10. Vale RD

    (2016) Phase separation of signaling molecules promotes T cell receptor signal transduction

    Science 352:595–599.

    https://doi.org/10.1126/science.aad9964

    • PubMed
    • Google Scholar
65. 1. Südhof TC
    2. Rothman JE

    (2009) Membrane fusion: grappling with SNARE and SM proteins

    Science 323:474–477.

    https://doi.org/10.1126/science.1161748

    • PubMed
    • Google Scholar
66. 1. Top D
    2. de Antueno R
    3. Salsman J
    4. Corcoran J
    5. Mader J
    6. Hoskin D
    7. Touhami A
    8. Jericho MH
    9. Duncan R

    (2005) Liposome reconstitution of a minimal protein-mediated membrane fusion machine

    The EMBO Journal 24:2980–2988.

    https://doi.org/10.1038/sj.emboj.7600767

    • PubMed
    • Google Scholar
67. 1. Top D
    2. Barry C
    3. Racine T
    4. Ellis CL
    5. Duncan R

    (2009) Enhanced fusion pore expansion mediated by the trans-acting endodomain of the reovirus FAST proteins

    PLOS Pathogens 5:e1000331.

    https://doi.org/10.1371/journal.ppat.1000331

    • PubMed
    • Google Scholar
68. 1. Valansi C
    2. Moi D
    3. Leikina E
    4. Matveev E
    5. Graña M
    6. Chernomordik LV
    7. Romero H
    8. Aguilar PS
    9. Podbilewicz B

    (2017) Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

    Journal of Cell Biology 216:571–581.

    https://doi.org/10.1083/jcb.201610093

    • PubMed
    • Google Scholar
69. 1. von Besser K
    2. Frank AC
    3. Johnson MA
    4. Preuss D

    (2006) Arabidopsis HAP2 (GCS1) is a sperm-specific gene required for pollen tube guidance and fertilization

    Development 133:4761–4769.

    https://doi.org/10.1242/dev.02683

    • PubMed
    • Google Scholar
70. 1. Wakimoto H
    2. Shimodo M
    3. Satoh Y
    4. Kitagawa Y
    5. Takeuchi K
    6. Gotoh B
    7. Itoh M

    (2013) F-actin modulates measles virus cell-cell fusion and assembly by altering the interaction between the matrix protein and the cytoplasmic tail of hemagglutinin

    Journal of Virology 87:1974–1984.

    https://doi.org/10.1128/JVI.02371-12

    • PubMed
    • Google Scholar
71. 1. Welch MD
    2. Way M

    (2013) Arp2/3-mediated actin-based motility: a tail of pathogen abuse

    Cell Host & Microbe 14:242–255.

    https://doi.org/10.1016/j.chom.2013.08.011

    • PubMed
    • Google Scholar
72. 1. Wilcox GE
    2. Compans RW

    (1982) Cell fusion induced by Nelson bay virus

    Virology 123:312–322.

    https://doi.org/10.1016/0042-6822(82)90264-1

    • PubMed
    • Google Scholar
73. 1. Wilson IA
    2. Skehel JJ
    3. Wiley DC

    (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution

    Nature 289:366–373.

    https://doi.org/10.1038/289366a0

    • PubMed
    • Google Scholar
74. 1. Wurth MA
    2. Schowalter RM
    3. Smith EC
    4. Moncman CL
    5. Dutch RE
    6. McCann RO

    (2010) The actin cytoskeleton inhibits pore expansion during PIV5 fusion protein-promoted cell-cell fusion

    Virology 404:117–126.

    https://doi.org/10.1016/j.virol.2010.04.024

    • PubMed
    • Google Scholar
75. 1. Yang Y
    2. Zhang Y
    3. Li WJ
    4. Jiang Y
    5. Zhu Z
    6. Hu H
    7. Li W
    8. Wu JW
    9. Wang ZX
    10. Dong MQ
    11. Huang S
    12. Ou G

    (2017) Spectraplakin induces positive feedback between fusogens and the actin cytoskeleton to promote Cell-Cell fusion

    Developmental Cell 41:107–120.

    https://doi.org/10.1016/j.devcel.2017.03.006

    • PubMed
    • Google Scholar
76. 1. Zeev-Ben-Mordehai T
    2. Vasishtan D
    3. Siebert CA
    4. Grünewald K

    (2014) The full-length cell-cell fusogen EFF-1 is monomeric and upright on the membrane

    Nature Communications 5:3912.

    https://doi.org/10.1038/ncomms4912

    • PubMed
    • Google Scholar
77. 1. Zhang Q
    2. Vashisht AA
    3. O'Rourke J
    4. Corbel SY
    5. Moran R
    6. Romero A
    7. Miraglia L
    8. Zhang J
    9. Durrant E
    10. Schmedt C
    11. Sampath SC
    12. Sampath SC

    (2017) The microprotein minion controls cell fusion and muscle formation

    Nature Communications 8:15664.

    https://doi.org/10.1038/ncomms15664

    • PubMed
    • Google Scholar
78. 1. Zheng QA
    2. Chang DC

    (1990) Dynamic changes of microtubule and actin structures in CV-1 cells during electrofusion

    Cell Motility and the Cytoskeleton 17:345–355.

    https://doi.org/10.1002/cm.970170409

    • PubMed
    • Google Scholar

Author details

1. Ka Man Carmen Chan

   1. UC Berkeley–UC San Francisco Graduate Group in Bioengineering, Berkeley, United States
   2. Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States

   Contribution

   Conceptualization, Resources, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-8595-9725

2. Sungmin Son

   Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States

   Contribution

   Conceptualization, Funding acquisition, Investigation, Methodology, Writing - review and editing

   Competing interests

   No competing interests declared

3. Eva M Schmid

   Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States

   Contribution

   Conceptualization, Funding acquisition, Writing - review and editing

   Competing interests

   No competing interests declared

4. Daniel A Fletcher

   1. UC Berkeley–UC San Francisco Graduate Group in Bioengineering, Berkeley, United States
   2. Department of Bioengineering & Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States
   3. Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, United States
   4. Chan Zuckerberg Biohub, San Francisco, United States

   Contribution

   Conceptualization, Supervision, Funding acquisition, Writing - original draft, Project administration, Writing - review and editing

   For correspondence

   fletch@berkeley.edu

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-1890-5364

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