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When Hse1p–Vps27p does not bind Ub (top), Ub-tagged proteins (green) escape the vacuole (red).

Piper/Macmillan

Patricia Bilodeau, Robert Piper, and colleagues (University of Iowa, Iowa City, IA) have identified an endosomal receptor complex that pushes proteins into the lumen of endosomes destined for the vacuole. This internalization step represents another possible site of regulation for controlling receptor activity.

Receptors and other plasma membrane proteins bound for destruction are tagged with one or more ubiquitin (Ub) molecules before they are internalized in vesicles that fuse with early endosomes. To be fully degraded when the endosome fuses with the vacuole, the tagged proteins must bud off a second time to form a multivesiculated body (MVB)—a structure that has vesicles inside the lumen of the endosome. Proteins that escape this step never reach the inside of the vacuole and may still be recycled back to the cell surface....

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