Recommended Article (F1000 Prime) cTAGE5 and Sec12

I recommended the following article for F1000 Prime.

Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export.
K Saito, K Yamashiro, N Shimazu, T Tanabe, K Kontani and T Katada
J Cell Biol 2014 Sep 8 DOI: 10.1083/jcb.201312062

This work has some significant implications for the organization and mechanisms of secretory cargo export from the endoplasmic reticulum (ER). Assembly of the COPII complex that drives this event occurs at spatially restricted sites on the ER membrane known as ER exit sites (ERES). Here, Saito and colleagues show that cTAGE5, a protein shown previously to be required for collagen export, is required to localize Sec12 to ERES. This is important because Sec12 is the initiator of COPII assembly. Sec12 acts as the guanine nucleotide exchange factor for Sar1, which, in its GTP-bound state, recruits the rest of the COPII complex. Previous work {1} had shown that Sec12 was localized across the ER with possibly some minor concentration in ERES. Here, using newly developed antibodies, the authors show that Sec12 is highly enriched at ERES, dependent on the presence of cTAGE5. The authors then tie this to the role of cTAGE5 in driving collagen secretion, notably of collagen VII. Perhaps more significantly, this work could implicate cTAGE5, and by extension its partner TANGO1, as a more fundamental component of the COPII budding machinery. cTAGE5 does not appear to be absolutely required for ongoing transport of many cargoes; there does, however, appear to be a kinetic delay in the delivery of cargo from the ER to Golgi.
There are some other important features to the data: cTAGE5 doesn’t appear to be required for the localization of Sec16 to ERES, nor is collagen VII required to maintain cTAGE5 at ERES (which is consistent with roles beyond that in collagen VII secretion alone). cTAGE5 also appears to be interdependent with its known interacting partner, TANGO1, for much of its functions.
The conclusion is really that cTAGE5 bridges Sec12 and TANGO1. The key question remains how these interactions are controlled and integrated with other factors known to be required for COPII function, especially in the context of collagen secretion.

{1} The mammalian guanine nucleotide exchange factor mSec12 is essential for activation of the Sar1 GTPase directing endoplasmic reticulum export. Weissman JT, Plutner H, Balch WE. Traffic 2001 Jul; 2(7):465-75 PMID: 11422940

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