Like cows wandering away from the herd, ER proteins sometimes stray. Shibuya et al. identify a protein complex that helps return them to the ER.

ER resident proteins occasionally break free and end up in the Golgi apparatus, where they may be shunted into the secretory pathway. Researchers already knew about one mechanism for retrieving these escapees. Proteins carrying the KDEL motif ride back to the ER in COPI-coated vesicles, which sport a KDEL receptor. How cells recapture ER proteins that lack the KDEL motif was unclear.

Shibuya et al. found that a complex of two Golgi proteins, Erv41 and Erv46, performs this function. Deleting Erv41 from yeast cells caused a 60% decrease in the levels of one ER protein, Gls1. In these cells, the escaped Gls1 was eventually secreted or directed to the vacuole for destruction.

The early portions of the Golgi apparatus are slightly acidic. By altering pH levels in vitro, Shibuya et al. determined that the Erv41–Erv46 complex releases Gls1 if the pH rises much above 6. The team confirmed the pH effect by dosing yeast cells with bafilomycin A1, which makes the Golgi less acidic. The cells began to secrete Gls1, indicating the protein wasn’t being recovered.

Erv46 carries a sequence that binds to the COPI coat, and the complex returns Gls1 to the ER by corralling it into COPI vesicles. The researchers found that the complex also retrieves several other ER proteins, including Fpr2 and Vps62.

, et al
J. Cell Biol.

Author notes

Text by Mitch Leslie