CELLUBREVIN IS A UBIQUITOUS TETANUS-TOXIN SUBSTRATE HOMOLOGOUS TO A PUTATIVE SYNAPTIC VESICLE FUSION PROTEIN

TETANUS toxin inhibits neurotransmitter release by selectively blockin g fusion of synaptic vesicles1,2. Recently tetanus toxin was shown to proteolytically degrade synaptobrevin II (also named VAMP-2), a synapt ic vesicle-specific protein3,4, in vitro and in nerve terminals5,6. As targets of tetanus toxin, synaptobrevins probably function in the exo cytotic fusion of synaptic vesicles. Here we describe a new synaptobre vin homologue, cellubrevin, that is present in all cells and tissues t ested and demonstrate that it is a membrane trafficking protein of a c onstitutively recycling pathway. Like synaptobrevin II, cellubrevin is proteolysed by tetanus toxin light chain in vitro and after transfect ion. Our results suggest that constitutive and regulated vesicular pat hways use homologous proteins for membrane trafficking, probably for m embrane fusion at the plasma membrane, indicating a greater mechanisti c and evolutionary similarity between these pathways than previously t hought.