MINTS, MUNC18-INTERACTING PROTEINS IN SYNAPTIC VESICLE EXOCYTOSIS

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is r equired for synaptic vesicle exocytosis. We have now identified two Mu nc18-1-interacting proteins called Mint1 and Mint2 that may mediate th e 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 ar e part of a multimeric complex containing Munc18-1 and syntaxin that l ikely functions as an intermediate in synaptic vesicle docking/fusion. The phosphotyrosine-binding domain specifically binds to phosphatidyl inositol phosphates known to be produced during vesicle exocytosis (Ha y, J. C., Fisette, P. L., Jenkins, G. H., Fukami, K., Takonawa, T., An derson, R. A., and Martin, T. F. J. (1995) Nature 374, 173-177). Our d ata suggest a model whereby local production of phosphatidylinositol p hosphates may trigger the binding of vesicles to the active zone via t he Minc.Munc18-1 complex in conjunction with syntaxin 1.