Mints, Munc18-interacting Proteins in Synaptic Vesicle Exocytosis*
- From the Howard Hughes Medical Institute and the Department of Molecular Genetics, University of Texas Southwestern Medical School, Dallas, Texas 75235
Abstract
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.
Footnotes
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↵* 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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF029105–AF029108.
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↵‡ Supported by postdoctoral fellowships from the HFSP, the TOYOBO Biotechnology Foundation, and the Takeda Medical Foundation.
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↵§ To whom correspondence should be addressed. E-mail:TSudho{at}Mednet.SWMED.edu.
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↵1 M. Verhage and T. C. Südhof, unpublished data.
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↵2 The abbreviations used are: GST, glutathioneS-transferase; PTB domain, phosphotyrosine-binding domain; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; PAGE, polyacrylamide gel electrophoresis; PIP, phosphatidylinositol phosphate; PIP2, phosphatidylinositol bisphosphate.
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- Received September 16, 1997.
- Revision received October 8, 1997.
