DIFFERENTIAL EXPRESSION OF SYNAPTIC VESICLE PROTEIN-2 (SV2) ISOFORMS

The synaptic vesicle proteins SV2A and SV2B (SV2 = synaptic vesicle pr otein 2) are two highly related proteins belonging to a family of tran sporters. As a first step toward identifying the function of the SV2 p roteins, we examined the expression of SV2A and SV2B in the rat brain by in situ hybridization, immunohistochemistry, and immunoprecipitatio n with isoform-specific antibodies. These analyses revealed that one i soform, SV2A, is expressed ubiquitously throughout the brain at varyin g levels. The other isoform, SV2B, has a more limited distribution wit h varying degrees of coexpression with SV2A. Immunoprecipitation of br ain synaptic vesicles with isoform-specific antibodies followed by Wes tern analyses suggests that both isoforms can be present on the same s ynaptic vesicle. The expression of the SV2 proteins did not correlate either with neurotransmitter phenotype or with the expression of other synaptic vesicle protein isoforms. SV2B expression was observed to ch ange during development; it is more widely expressed in the immature b rain and is found in cells that have yet to establish synaptic contact s. The ubiquitous and overlapping expression of the SV2s suggests that they perform a function common to all synaptic vesicles. Variable and changing coexpression of the SV2 isoforms may indicate that SV2 funct ion is regulated by the isoform composition of synaptic vesicles. The observation that the synaptic vesicle proteins, all occurring in multi ple isoforms, are differentially expressed with respect to each other indicates that up to 90 different vesicle types are possible.