F1000 evaluation: ER Cargo Properties Specify a Requirement for COPII Coat Rigidity Mediated by Sec13p

I have just evaluated the following paper from Faculty of 1000:

ER Cargo Properties Specify a Requirement for COPII Coat Rigidity Mediated by Sec13p.

Alenka Čopič, Catherine F. Latham, Max A. Horlbeck, Jennifer G. D’Arcangelo, Elizabeth A. Miller
Science 2012
PMID 22300850
DOI 10.1126/science.1215909

This fascinating paper defines a link between structural features of an assembling vesicle coat complex with the cargo to be incorporated. Sec13 is an essential component of the COPII coat that drives export of secretory cargo from the endoplasmic reticulum (ER). The requirement for this gene can be bypassed by a series of suppressor mutations in mutants known as Bypass-Sec13 (Bst) (first identified by Chris Kaiser’s lab {1}). The authors took a genetic approach in yeast (using synthetic gene arrays) to identify all of the genes that alleviate the defects caused by loss of Sec13. As in the previous work from Kaiser et al., Miller and colleagues found that all identified genes relate to the synthesis and export of glycosylphosphatidylinositol (GPI)-anchored proteins from the ER. This provides a direct link between the presence of cargo in the inner leaflet (where GPI-anchored proteins reside) and the role of the coat complex on the cytosolic face of the membrane in the formation of vesicles. It was hypothesized that the absence of these cargo proteins from the sites of vesicle formation leads to more readily deformable membranes, eliminating the need for Sec13, the conclusion here being that Sec13 is required to enhance rigidity of the COPII coat to drive membrane deformation under normal conditions. Using a series of elegant mutations in Sec13 and its binding partner Sec31, the authors show quite convincingly that this model of structural rigidity holds true. The finding that Sec13 is required in this way also provides some insight into the apparent selective requirement for Sec13 in the secretion of procollagen (see ref {2}, on which I appear as an author). The structural rigidity of the procollagen triple helix might dictate the requirement for similar structural rigidity within the assembling COPII coat.


{1} Elrod-Erickson and Kaiser, Mol Biol Cell 1996, 7:1043-58 [PMID:8862519].

{2} Townley et al. J Cell Sci 2008, 121:3025-34 [PMID:18713835].


The original evaluation can be found here.