Fast, synchronous exocytosis: the dyad model.

講演要旨

Fast, synchronous exocytosis of chemical neurotransmitters is the primary mechanism of communication between neurons and their synaptic targets. Four proteins have been identified as likely contributors to the membrane fusion event that underlies the Ca2+-dependent release of neurotransmitters. The synaptic vesicle protein, synaptotagmin1 (syt), is widely acknowledged to be the Ca2+ sensor for this process. However, it is not yet clear what syt does once it binds Ca2+. Of the dozens of published models, most propose that syt regulates the bundling or “zippering” of SNARE proteins. SNAREs, a trio of proteins, include the vesicular SNARE, synaptobrevin2 and two plasma membrane proteins, syntaxin1 and SNAP-25 (known as target SNAREs). It is widely inferred that once a synaptic vesicle approaches within ~10 nm of the plasma membrane, the N-terminal regions of synaptobrevin2 and syntaxin1 can interact and begin to form a coiled-coil structure. Subsequently, SNAP-25 contributes two separate domains to this complex which then zippers into a four-helix bundle. The formation of the SNARE complex is almost universally regarded as the molecular event driving the fusion of the synaptic vesicle membrane with the plasma membrane. However, none of the models of this process clearly explains how SNARE zippering drives membrane fusion. The dyad model of membrane fusion was developed as an alternative to SNARE models. It envisions syt serving both as the Ca2+ sensor for exocytosis and as a catalyst of membrane fusion. This seminar will present a step-by-step outline of how syt can fulfill these dual roles.