Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.
Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1. Mint proteins are detectable only in brain and are composed of an N-terminal sequence that binds Munc18-1, a middle phosphotyrosine-binding domain, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane. In brain, Mint proteins are part of a multimeric complex containing Munc18-1 and syntaxin that likely functions as an intermediate in synaptic vesicle docking/fusion. The phosphotyrosine-binding domain specifically binds to phosphatidylinositol phosphates known to be produced during vesicle exocytosis (Hay, J. C., Fisette, P. L., Jenkins, G. H., Fukami, K., Takonawa, T., Anderson, R. A., and Martin, T. F. J. (1995) Nature 374, 173-177). Our data suggest a model whereby local production of phosphatidylinositol phosphates may trigger the binding of vesicles to the active zone via the Mint.Munc18-1 complex in conjunction with syntaxin 1.
Okamoto
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Howard Hughes Medical Institute and the Department of Molecular Genetics, University of Texas Southwestern Medical School, Dallas, Texas 75235, USA.
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001923:Brain Chemistry; D019556:COS Cells; D015820:Cadherins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D005089:Exocytosis; D015723:Gene Library; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013572:Synaptic Vesicles / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
C079091:APBA1 protein, human; C491636:APBA2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; C513072:Apba1 protein, mouse; C513071:Apba1 protein, rat; C491635:Apba2 protein, mouse; C109650:Apba2 protein, rat; D015820:Cadherins; D002352:Carrier Proteins; D008565:Membrane Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; C497931:SEC1 protein, S cerevisiae; C494208:SNAP25 protein, human; C494212:STX1A protein, human; C497937:STXBP1 protein, human; D029701:Saccharomyces cerevisiae Proteins; C494209:Snap25 protein, mouse; C494210:Snap25 protein, rat; C494214:Stx1a protein, mouse; C494213:Stx1a protein, rat; C497938:Stxbp1 protein, mouse; C497939:Stxbp1 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins