Abstract
Munc13-1 and DOC2 have been implicated in the regulation of exocytosis. Here we demonstrate in vivo that these two proteins undergo a transient phorbol ester-mediated and protein kinase C-independent interaction, resulting in the translocation of DOC2 from a vesicular localization to the plasma membrane. The translocation of DOC2 is dependent upon the DOC2 Munc interacting domain that binds specifically to Munc13-1, whereas the association of DOC2 with intracellular membranes is dependent on its C2 domains. This is the first direct in vivo demonstration of a protein-protein interaction between two presynaptic proteins and may represent a molecular basis for phorbol ester-dependent enhancement of exocytosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids
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Animals
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Benzophenanthridines
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Brain / metabolism
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / physiology
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Enzyme Inhibitors / pharmacology
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Exocytosis / drug effects
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Green Fluorescent Proteins
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Humans
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins / metabolism
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Mice
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Open Reading Frames
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Phenanthridines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Rats
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Recombinant Fusion Proteins / metabolism
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Tetradecanoylphorbol Acetate / pharmacology*
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Transfection
Substances
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Alkaloids
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Benzophenanthridines
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Calcium-Binding Proteins
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DOC2A protein, human
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DOC2B protein, human
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Doc2a protein, mouse
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Doc2a protein, rat
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Nerve Tissue Proteins
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Phenanthridines
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Recombinant Fusion Proteins
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UNC13B protein, human
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Unc13a protein, rat
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Unc13b protein, mouse
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Green Fluorescent Proteins
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chelerythrine
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Protein Kinase C
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Tetradecanoylphorbol Acetate