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Review
. 2019 Aug:59:104-111.
doi: 10.1016/j.ceb.2019.04.002. Epub 2019 May 21.

Coat flexibility in the secretory pathway: a role in transport of bulky cargoes

Joshua Hutchings  1 , Giulia Zanetti  2
Affiliations
Review

Coat flexibility in the secretory pathway: a role in transport of bulky cargoes

Joshua Hutchings et al. Curr Opin Cell Biol. 2019 Aug.

Abstract

Membrane trafficking in eukaryotic cells is a highly dynamic process, which needs to adapt to a variety of cargo proteins. The COPII coat mediates ER export of thousands of proteins with a wide range of sizes by generating coated membrane vesicles that incapsulate cargo. The process of assembly and disassembly of COPII, regulated by GTP hydrolysis, is a major determinant of the size and shape of transport carriers. Here, we analyse our knowledge of the COPII coat architecture and it assembly/disassembly dynamics, and link coat flexibility to the role of COPII in transport of large cargoes. We propose a common mechanism of action of regulatory factors that modulate COPII GTP hydrolysis cycle to promote budding.

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Conflict of interest statement

Conflict of interest statement

Nothing declared.

Figures

Figure 1
Figure 1. An overview of the secretory pathway in metazoan cells.
Budding from the ER to the ERGIC is mediated by the double-layered COPII coat (inner layer in blue and outer layer in red), while ER retrieval is mediate by the COPI coat (yellow). Transport throughout the Golgi is mediated by the COPI coat.
Figure 2
Figure 2. Structure of the COPII coat.
Inner coat assembly is mediated by the Sec23 (blue) and Sar1 (yellow) subunits, when Sar1 is in the GTP-bound state. Sec24 (green) mediates incorporation of most cargo proteins (pink). Sec31 (red) templates inner coat assembly by binding at the interface between inner coat subunits through PPP motifs in its disordered C-terminal region. Sec13 (grey)-Sec31 rods themselves assemble to for cages.
Figure 3
Figure 3. COPII assembly/disassembly equilibrium as a major determinant of budding.
Assembly on membranes is initiated upon GTP exchange on Sar1. Coat assembly leads to GTP hydrolysis. In our model, the speed of GTP hydrolysis determines whether the resulting ratio between assembly and disassembly of inner and outer coat is sufficient to productively remodel membranes into smaller carriers. We propose this might be dependent on how easily deformable the membrane is (e.g. on initial curvature, or type of cargo).
Figure 4
Figure 4. Model for COPII-mediated Procollagen ER export.
When large cargo needs to be transported, COPII assembly is stabilised at the base of the budding carrier by rings of TANGO1 that promote inner coat assembly through multiple PPP motifs binding at the interface between Sec23 subunits. As the carrier grows, Sec31 displaces ER and procollagen-bound TANGO1 and eventually promotes disassembly of the coat. This is an elaboration of the model proposed in Ref. [23•], where we account for our recent finding that PPP bridges between inner coat subunits.
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