F1000 Evaluation (yes, another one)

This time, I have evaluated the following paper. Also on the F1000 site at: http://f1000.com/13688961

Kim SD, Pahuja KB, Ravazzola M, Yoon J, Boyadjiev SA, Hammamoto S, Schekman R, Orci L, Kim J.
The SEC23-SEC31 interface plays a critical role for export of procollagen from the endoplasmic reticulum.
J Biol Chem 2012
PMID 22298774 DOI 10.1074/jbc.M111.283382

This paper shows very nicely that the rate of Sar1 GTPase activity within the coat protein complex II (COPII) coat is central to the mechanism of packaging the large cargo procollagen at the endoplasmic reticulum (ER). It is unclear how the canonical COPII system is capable of packaging large cargoes such as procollagen (a 300nm rod-like structure) when it seems geared towards the production of 60-90nm vesicles. Here, Kim and colleagues exploit a mutation in the Sec23A component of the COPII coat that causes cranio-lenticulo-sutural dysplasia (a disease in which there is a pronounced failure to deposit collagenous extracellular matrix). During COPII assembly the inner (Sec23-Sec24) and outer (Sec13-Sec31) layers of the COPII coat both impact on Sar1 GTPase activity. The authors show that, compared to the wild-type protein, the Sec23A-M702V mutation causes an acceleration of Sar1 GTPase activity. This mutation lies at the contact site between Sec23 and Sec31, suggesting a role in coupling inner and outer layers of the coat.

These data support a model where slower assembly or greater stability of the COPII coat is required to package procollagen. The work also supports the notion that procollagen becomes encapsulated within a COPII-coated carrier, but visualization of such a carrier remains elusive.

This work builds very nicely on previous work in this area which was summarized in this recent review {1}.

References:

{1} Zanetti et al. Nat Cell Biol 2012, 14:221 [PMID:22298048].

Added note – you’ll see I have been reading a lot about collagen export recently.

One more to come soon.

Advertisements