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J Biol Chem. 2000 May 19;275(20):15271-8.

Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15.

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  • 1Department of Neurobiology and Anatomy, and The W. M. Keck Center for the Neurobiology of Learning and Memory, University of Texas Medical School, Houston, Texas 77030, USA.


Hrs-2, via interactions with SNAP-25, plays a regulatory role on the exocytic machinery. We now show that Hrs-2 physically interacts with Eps15, a protein required for receptor-mediated endocytosis. The Hrs-2/Eps15 interaction is calcium dependent, inhibited by SNAP-25 and alpha-adaptin, and results in the inhibition of receptor-mediated endocytosis. Immunoelectron microscopy reveals Hrs-2 localization on the limiting membrane of multivesicular bodies, organelles in the endosomal pathway. These data show that Hrs-2 regulates endocytosis, delineate a biochemical pathway (Hrs-2-Eps15-AP2) in which Hrs-2 functions, and suggest that Hrs-2 acts to provide communication between endo- and exocytic processes.

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