Differential expression of synaptic vesicle protein 2 (SV2) isoforms

Abstract

The synaptic vesicle proteins SV2A and SV2B (SV2 = synaptic vesicle protein 2) are two highly related proteins belonging to a family of transporters. As a first step toward identifying the function of the SV2 proteins, we examined the expression of SV2A and SV2B in the rat brain by in situ hybridization, immunohistochemistry, and immunoprecipitation with isoform-specific antibodies. These analyses revealed that one isoform, SV2A, is expressed ubiquitously throughout the brain at varying levels. The other isoform, SV2B, has a more limited distribution with varying degrees of coexpression with SV2A. Immunoprecipitation of brain synaptic vesicles with isoform-specific antibodies followed by Western analyses suggests that both isoforms can be present on the same synaptic 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 change during development; it is more widely expressed in the immature brain and is found in cells that have yet to establish synaptic contacts. 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 function is regulated by the isoform composition of synaptic vesicles. The observation that the synaptic vesicle proteins, all occurring in multiple isoforms, are differentially expressed with respect to each other indicates that up to 90 different vesicle types are possible.

Synaptic Vesicle Protein SV2B, but Not SV2A, Is Predominantly Expressed and Associated with Microvesicles in Rat Pinealocytes

“…PCI2 cells express only SV2A, i.e., not SV2B, consistent with the previous observation (Bajjalieh et al, 1994) (Fig. 7A and B).…”

“…The migration pattern of the positive protein bands on the SDS gel was very similar to those previously reported (Bajjalieh et al, 1992(Bajjalieh et al, , 1993(Bajjalieh et al, , 1994. Treatment with antigenic peptides during immunodecoration abolished the immunoreactivity (Fig.…”

“…nucleotide and deduced amino acid sequences of the brain and pineal gland DNA fragments completely matched those of the corresponding sequences of SV2A and SV2B (Bajjalieh et al, 1993(Bajjalieh et al, , 1994, respectively. These results suggested that both isoforms of SV2 are expressed in pineal gland.…”

“…Two isoforms, abbreviated as SV2A and SV2B, have been identified in mammals; the former consists of 742 amino acids and the latter of 683 amino acids, with 65% sequence homology (Bajjalieh et al, 1993(Bajjalieh et al, , 1994. SV2A is expressed in both peripheral endocrine cells and neurons, whereas SV2B was shown to be expressed only in neurons (Bajjalieh et al, 1993(Bajjalieh et al, , 1994.…”

Synaptic Vesicle Protein 2 (SV2) Isoforms

“…SV2A is widely distributed in the nervous system, in virtually all neurons. SV2B is also widely expressed in SV2A-containing neurons, although not as extensively as SV2A, whereas SV2C is only observed in a small number of neurons in a few brain areas (Bajjalieh et al, 1993;1994;Janz et al, 1998;Janz and Sudhof, 1999). The study of these isoforms would aid in the understanding of the role of this protein in secretions of mammary glands and breast cancer development in order to detect opportunely breast tumors and to treat them with novel and specific therapies.…”