By collecting at specific sites in the ER the protein Sec12 permits collagen to depart from the organelle, Saito et al. show. The discovery brings researchers closer to explaining the mystery of how cells secrete large cargoes.

Cells that make collagen face a challenge. The COPII-coated vesicles that typically transport secretory proteins from the ER are 60–90 nm across, but collagen molecules are up to 400 nm long. Yet studies indicate that collagen secretion requires the molecular machinery that creates COPII vesicles. Researchers suspect that certain proteins modify this machinery so that it can handle larger cargo, but they aren’t sure which proteins do the job.

Saito et al. searched for proteins in mammalian cells that bind to cTAGE5, a collagen receptor in the ER membrane. They identified Sec12, which activates the on–off switch for the COPII machinery, Sar1. The researchers found that cTAGE5 concentrates Sec12 at the spots where collagen leaves the ER. Moreover, if cTAGE5 doesn’t guide Sec12 to these locations, cells can’t secrete collagen VII, but they can secrete other proteins.

Although researchers knew that Sec12 localized to the ER, this study reveals that the protein accumulates at collagen exit sites and is essential for the protein’s release. How collagen leaves the ER remains unclear, but Sec12 might stimulate the process by activating large amounts of Sar1 at the exit sites.

References

Saito
,
K.
, et al
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2014
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J. Cell Biol.
.

Author notes

Text by Mitch Leslie