TANGO1 builds a machine for collagen export by recruiting and spatially organizing COPII, tethers and membranes
Abstract
Collagen export from the endoplasmic reticulum (ER) requires TANGO1, COPII coats, and retrograde fusion of ERGIC membranes. How do these components come together to produce a transport carrier commensurate with the bulky cargo collagen? TANGO1 is known to form a ring that corrals COPII coats and we show here how this ring or fence is assembled. Our data reveal that a TANGO1 ring is organized by its radial interaction with COPII, and lateral interactions with cTAGE5, TANGO1-short or itself. Of particular interest is the finding that TANGO1 recruits ERGIC membranes for collagen export via the NRZ (NBAS/RINT1/ZW10) tether complex. Therefore, TANGO1 couples retrograde membrane flow to anterograde cargo transport. Without the NRZ complex, the TANGO1 ring does not assemble, suggesting its role in nucleating or stabilising of this process. Thus, coordinated capture of COPII coats, cTAGE5, TANGO1-short, and tethers by TANGO1 assembles a collagen export machine at the ER.
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Funding
Ministerio de Economía y Competitividad (BFU2013-44188-P)
- Vivek Malhotra
AEI/FEDER, UE
- Maria F Garcia-Parajo
Human Frontier Science Program (GA RGP0027/2012)
- Maria F Garcia-Parajo
Cordis (EC FP7-NANO-VISTA (GA 288263)
- Maria F Garcia-Parajo
LaserLab 4 Europe (GA 654148)
- Maria F Garcia-Parajo
Ministerio de Economía y Competitividad (CSD2009-00016)
- Vivek Malhotra
Barcelona Institute of Science and Technology (BIST-IGNITE-eTANGO)
- Ishier Raote
- Felix Campelo
- Vivek Malhotra
Ministerio de Economía y Competitividad (SEV-2012-0208)
- Vivek Malhotra
Ministerio de Economía y Competitividad (SEV-2015-240522)
- Vivek Malhotra
Ministerio de Economía y Competitividad (FIS2014-56107-R)
- Maria F Garcia-Parajo
Ministerio de Economía y Competitividad (MDM-2015-0502)
- Vivek Malhotra
Ministerio de Economía y Competitividad (BFU2015-73288-JIN)
- Maria F Garcia-Parajo
Fundacion Privada Cellex
- Maria F Garcia-Parajo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Raote 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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Further reading
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- Cell Biology
- Structural Biology and Molecular Biophysics
We have previously shown TANGO1 organises membranes at the interface of the endoplasmic reticulum (ER) and ERGIC/Golgi (Raote et al., 2018). TANGO1 corrals retrograde membranes at ER exit sites to create an export conduit. Here the retrograde membrane is, in itself, an anterograde carrier. This mode of forward transport necessitates a mechanism to prevent membrane mixing between ER and the retrograde membrane. TANGO1 has an unusual membrane helix organisation, composed of one membrane-spanning helix (TM) and another that penetrates the inner leaflet (IM). We have reconstituted these membrane helices in model membranes and shown that TM and IM together reduce the flow of lipids at a region of defined shape. We have also shown that the helices align TANGO1 around an ER exit site. We suggest this is a mechanism to prevent membrane mixing during TANGO1-mediated transfer of bulky secretory cargos from the ER to the ERGIC/Golgi via a tunnel.
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- Biochemistry and Chemical Biology
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