Figure 1.

The mechanism of unconventional protein secretion of Acb1. CUPS assemble in response to starvation near the ER exit sites in yeast. Acb1 is acetylated and binds acyl-CoA, and these reactions assist its targeting to CUPS. The biogenesis of CUPS requires Grh1, Bug1, and Vps34 (in green). A new class of vesicular intermediates is generated at the CUPS by a COPII-independent process. These vesicles containing Acb1 on their cytoplasmic face fuse with the endosomes by a Tlg2- and Ypt6-dependent process. Acb1, which is deposited on the cytoplasmic face of an endosome is then internalized by an ESCRT (Vps23 and Vps4)-dependent process. The t-SNARE Sso1 mediates the fusion of resulting MVB with the plasma membrane to release Acb1-containing exosome-like vesicles into the extracellular space where they lyse to release Acb1.