Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adenosine Triphosphatases / analysis
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Adenosine Triphosphatases / metabolism*
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Animals
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Brain / metabolism
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Calcium / metabolism
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Calcium-Binding Proteins / metabolism*
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Cerebellum / metabolism
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Endocytosis / physiology*
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Endosomal Sorting Complexes Required for Transport
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Endosomes / metabolism*
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Endosomes / ultrastructure
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins
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Kinetics
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Membrane Proteins*
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Microscopy, Immunoelectron
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism*
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Neurons / ultrastructure
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Phosphoproteins / metabolism*
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Rats
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Receptors, Cell Surface / physiology*
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Recombinant Proteins / metabolism
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Signal Transduction
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Synaptosomal-Associated Protein 25
Substances
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Adaptor Proteins, Signal Transducing
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Calcium-Binding Proteins
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EPS15 protein, human
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Endosomal Sorting Complexes Required for Transport
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Phosphoproteins
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Receptors, Cell Surface
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Recombinant Proteins
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SNAP25 protein, human
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Snap25 protein, rat
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Synaptosomal-Associated Protein 25
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Adenosine Triphosphatases
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Hgs protein, rat
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Calcium