Bruns et al. describe how several proteins required for an unconventional secretory pathway gather together in a novel membrane compartment.

The Acyl-CoA binding protein Acb1 is secreted by starving budding yeast, but, unlike most secretory proteins, Acb1 doesn't pass through the ER and Golgi on its way to the cell surface. The details of Acb1's alternative route are unknown, but a diverse set of proteins mediate its journey. Components required for Acb1 secretion include autophagy proteins (such as Atg8 and Atg9), proteins that deliver cargo to multivesicular bodies (for example, Vps23), and Grh1, a homologue of a mammalian Golgi protein.

Bruns et al. found that, upon starvation, Grh1 concentrated in membrane compartments near ER exit sites. These structures didn't contain markers of the ER, Golgi, or endosomes, but they did contain Vps23, Atg8, and Atg9, as well as the phosphoinositide PI(3)P. Blocking PI(3)P synthesis or deleting Grh1 prevented the formation of these compartments in starving yeast.

By electron microscopy, the Grh1-containing membranes appeared cup-shaped, leading the authors to name them compartments for unconventional protein secretion or CUPS. Their shape and the presence of Atg8 and Atg9 are reminiscent of autophagosome precursors, but Bruns et al. found that CUPS weren't formed in response to the autophagy-inducing drug rapamycin, suggesting that CUPS are a novel, albeit related, compartment. Senior author Vivek Malhotra says that the identification of CUPS gives researchers a handle to uncover other steps in Acb1 secretion. CUPS may engulf Acb1 in the cytoplasm and deliver it to the plasma membrane, either directly or via fusion with secretory endosomes.


et al
J. Cell Biol.