Before the fusion of synaptic vesicles with the plasma membrane, a pro
tein complex is thought to form between VAMP-an integral membrane prot
ein of the vesicle-and two proteins associated with the plasma membran
e, SNAP-25 and syntaxin. The yeast two-hybrid interaction cloning syst
em has now been used to identify additional proteins from Aplysia that
interact directly with VAMP. A 33-kilodalton membrane protein, termed
VAP-33 (VAMP-associated protein of 33 kilodaltons), was identified wh
ose corresponding messenger RNA was detected only in the central nervo
us system and the gill of Aplysia. Presynaptic injection of antibodies
specific for VAP-33 inhibited synaptic transmission, which suggests t
hat VAP-33 is required for the exocytosis of neurotransmitter.