Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15.
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.
Bean
A J
AJ
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, USA.
Davanger
S
S
Chou
M F
MF
Gerhardt
B
B
Tsujimoto
S
S
Chang
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008565:Membrane Proteins; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D050825:Synaptosomal-Associated Protein 25
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C486206:EPS15 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C494208:SNAP25 protein, human; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D000251:Adenosine Triphosphatases; C115505:Hgs protein, rat; D002118:Calcium