Molecular Mechanisms of Neurotransmitter Release 
membrane proteins. The primary structures of 
these proteins were determined in this labora- 
tory, and specific antibodies and different ex- 
pression systems are being used to probe their 
functional roles. 
Synaptophysin has a complex structure consist- 
ing of a homotrimer that spontaneously re-forms 
into a homohexamer upon reduction of its disul- 
fide bonds. Synaptotagmin and synaptobrevin are 
highly conserved synaptic vesicle proteins that 
we have also characterized in the fruit fly Dro- 
sophila melanogaster. Synaptotagmin contains 
two copies of a Ca^"^-binding domain found in 
protein kinase C. Recombinant synaptotagmin 
also avidly binds phospholipids, suggesting that 
it may have a role in the Ca^'^-regulated steps of 
synaptic vesicle exocytosis. 
The synapsins are the major phosphoproteins 
of the nerve terminal and interact with the cyto- 
skeleton in a phosphorylation-dependent man- 
ner. The four synapsins are the differentially 
spliced products of two separate genes. They are 
composed of mosaics of shared and unique do- 
mains and are differentially distributed among 
synapses. The synapsins presumably have a role 
in the vesicle traffic to and from the plasma mem- 
brane and may regulate the number of vesicles 
available for exocytosis. They are stoichiometri- 
cally phosphorylated at multiple sites by multi- 
ple protein kinases, as a function of the activation 
state of the nerve terminal. 
Together, our studies have characterized a siz- 
able portion of the synaptic vesicle proteins and 
are approaching the dissection of the synaptic ves- 
icle pathway in molecular terms. Our current in- 
vestigations of the interactions of synaptic vesicle 
proteins with other proteins of the synaptic nerve 
terminal are an attempt to understand the role of 
these proteins in regulating neurotransmitter 
release. 
440 
