IDENTIFICATION OF A NOVEL SYNTAXIN-BINDING AND SYNAPTOBREVIN VAMP-BINDING PROTEIN, SNAP-23, EXPRESSED IN NONNEURONAL TISSUES/

The specificity of vesicular transport is regulated, in part, by the i nteraction of a vesicle-associated membrane protein termed synaptobrev in/VAMP with a target compartment membrane protein termed syntaxin. Th ese proteins, together with SNAP-25 (synaptosome associated protein of 25 kDa), form a complex which serves as a binding site for the genera l membrane fusion machinery, Synaptobrevin/VAMP and syntaxin are ubiqu itously expressed proteins and are believed to be involved in vesicula r transport in mast (if not all) cells. However, SNAP-25 is present al most exclusively in the brain, suggesting that a ubiquitously expresse d homolog of SNAP-25 exists to facilitate transport vesicle/target mem brane fusion in other tissues, Using the yeast two-hybrid system, we h ave 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 th e general membrane fusion machinery and an important regulator of tran sport vesicle docking and fusion in all mammalian cells.