The specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed syntaxin. These proteins, together with SNAP-25 (synaptosomeassociated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are ubiquitously expressed proteins and are believed to be involved in vesicular transport in most (if not all) cells. However, SNAP-25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP-25 exists to facilitate transport vesicle/target membrane fusion in other tissues. Using the yeast two-hybrid system, we have identified a 23-kDa protein from human B lymphocytes (termed SNAP-23) that binds tightly to multiple syntaxins and synaptobrevins/ VAMPs in vitro. SNAP-23 is 59% identical with SNAP-25. Unlike SNAP-25, SNAP-23 was expressed in all tissues examined. These findings suggest that SNAP-23 is an essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion in all mammalian cells.A fundamental goal of cell biology is the elucidation of the molecular steps involved in intracellular protein transport. In general, this process involves the liberation of cargo-containing transport vesicles from "donor" membranes and the subsequent docking and fusion of these vesicles with target, or "acceptor" membranes (1). It is clear that vesicle docking and vesicle fusion are distinct processes mediated by distinct proteins (reviewed in Refs. 2 and 3). Since the general membrane fusion machinery (consisting of NSF 1 and SNAPs) nonspecifically catalyzes membrane fusion, the regulation of fusion between transport vesicles and specific acceptor membranes is thought to lie in the vesicle docking process. In the brain, synaptic vesicle docking is regulated in part by specific interactions of the synaptic vesicle protein synaptobrevin (also known as vesicle-associated membrane protein or VAMP) with the presynaptic plasma membrane-associated proteins syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa; not related to the SNAPs for NSF). Together these molecules form a stable complex which also functions as a SNAP receptor ("SNARE"). It is believed SNAPs and NSF bind to the SNARE complex at the transport vesicle/target membrane interface so that following vesicle docking membrane fusion can occur.A general model of protein transport in all cells, the SNARE hypothesis, proposes that the specificity of a particular transport step is regulated by the specific interaction of distinct VAMPs and syntaxins on transport vesicles and target (acceptor) membranes, respectively (4). There is considerable experimental evidence to support the SNARE hypothesis, including the demonstration that (a) different isoforms of syntaxin and VAMP exist, some of which can be localized to unique intracellu...

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