Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
Abstract
Integrin adhesion complexes (IACs) are integrin-based plasma membrane-associated compartments where cells sense environmental cues. The physical mechanisms and molecular interactions that mediate initial IAC formation are unclear. We found that both p130Cas ('Cas') and Focal adhesion kinase ('FAK') undergo liquid-liquid phase separation in vitro under physiologic conditions. Cas- and FAK- driven phase separation is sufficient to reconstitute kindlin-dependent integrin clustering in vitro with recombinant mammalian proteins. In vitro condensates and IACs in mouse embryonic fibroblasts (MEFs) exhibit similar sensitivities to environmental perturbations including changes in temperature and pH. Furthermore, mutations that inhibit or enhance phase separation in vitro reduce or increase the number of IACs in MEFs, respectively. Finally, we find that the Cas and FAK pathways act synergistically to promote phase separation, integrin clustering, IAC formation and partitioning of key components in vitro and in cells. We propose that Cas- and FAK- driven phase separation provides an intracellular trigger for integrin clustering and nascent IAC formation.
Data availability
If the article is accepted, all imaging data will be deposited in the Dryad database before publication.
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Synergistic Phase Separation of Two Pathways Promotes Integrin Clustering and Nascent Adhesion FormationDryad Digital Repository, doi:10.5061/dryad.9p8cz8wj0.
Article and author information
Author details
Funding
Damon Runyon Cancer Research Foundation (postdoctoral fellowship,DRG-2249-16)
- Lindsay B Case
- Michael K Rosen
Damon Runyon Cancer Research Foundation (Dale Frey Scientist Award,DFS-38-20)
- Lindsay B Case
Howard Hughes Medical Institute (Investigator)
- Michael K Rosen
Welch Foundation (I-1544)
- Michael K Rosen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Case et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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