Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

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Abstract

Endocytic protein trafficking is directed by sorting signals on cargo molecules that are recognized by cytosolic adaptor proteins. However, the steps necessary to segregate the variety of cargoes during endocytosis remain poorly defined. Using Caenorhabditis elegans, we demonstrate thatmultiple plasmamembrane endocytic adaptors function redundantly to regulate clathrin-mediated endocytosis and to recruit components of the endosomal sorting complex required for transport (ESCRT)machinery to the cell surface to direct the sorting of ubiquitin-modified substrates. Moreover, our data suggest that preassembly of cargoes with the ESCRT-0 complex at the plasma membrane enhances the efficiency of downstream sorting events in the endolysosomal system. In the absence of a heterooligomeric adaptor complex composed of FCHO, Eps15, and intersectin, ESCRT-0 accumulation at the cell surface is diminished, and the degradation of a ubiquitin- modified cargo slows significantlywithout affecting the rate of its clathrin-mediated internalization. Consistent with a role for the ESCRTmachinery during cargo endocytosis,we further showthat the ESCRT-0 complex accumulates at a subset of clathrin-coated pits on the surface of human cells.Our findings suggest a uniquemechanism by which ubiquitin-modified cargoes are sequestered into the endolysosomal pathway.

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Mayers, J. R., Wang, L., Pramanik, J., Johnson, A., Sarkeshik, A., Wang, Y., … Audhya, A. (2013). Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane. Proceedings of the National Academy of Sciences of the United States of America, 110(29), 11857–11862. https://doi.org/10.1073/pnas.1302918110

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