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J Biol Chem, Vol. 275, Issue 20, 15271-15278, May 19, 2000

Hrs-2 Regulates Receptor-mediated Endocytosis via Interactions with Eps15*

Andrew J. BeanDagger , Svend Davanger§, Marian F. Chou, Brenda Gerhardt, Susan Tsujimoto, and YuChieh Chang

From the Department 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 and the § Department of Cell Biology and Anatomy, University of Bergen, Bergen 5009, Norway

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.

* This work was supported in part by the Mallinckrodt Foundation and National Institutes of Health Grant MH058920.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Neurobiology and Anatomy, University of Texas Medical School, 6431 Fannin St., Rm. 7.208, Houston, TX 77030. Tel.: 713-500-5614; Fax: 713-500-0623; E-mail: abean@nba19.med.uth.tmc.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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