SVOP, AN EVOLUTIONARILY CONSERVED SYNAPTIC VESICLE PROTEIN SUGGESTS NOVEL TRANSPORT FUNCTIONS OF SYNAPTIC VESICLES

We describe a novel synaptic vesicle protein called SVOP that is dista ntly related to the synaptic vesicle proteins SV2A, SV2B, and SV2C (20 -22% sequence identity). Both SVOP and SV2 contain 12 transmembrane re gions. However, SV2 is highly glycosylated, whereas SVOP is not. Datab ank searches revealed that closely related homologs of SVOP are presen t in Caenorhabditis elegans and Drosophila (48% sequence identity), su ggesting that SVOP is evolutionarily ancient. In contrast, no inverteb rate orthologs of SV2 were detected. The sequences of SVOP and SV2 exh ibit homology with transport proteins, in particular with mammalian or ganic cation and anion transporters. SVOP and SV2 are more distantly r elated to eukaryotic and bacterial phosphate, sugar, and organic acid transporters. SVOP is expressed at detectable levels only in brain and endocrine cells where it is primarily localized to synaptic vesicles and microvesicles. SVOP is present in all brain regions, with particul arly high levels in large pyramidal neurons of the cerebral cortex. Im munocytochemical staining of adjacent rat brain sections for SVOP and SV2 demonstrated that SVOP and SV2 are probably coexpressed in most ne urons. Although the functions of SV2 and SVOP remain obscure, the evol utionary conservation of SVOP, its hydrophobic nature, and its homolog y to transporters strongly support a role in the uptake of a novel, as yet unidentified component of synaptic vesicles. Thus synaptic vesicl es contain two classes of abundant proteins with 12 transmembrane regi ons that are related to transporters, nonglycosylated SVOP and highly glycosylated SV2, suggesting that the transport functions of synaptic vesicles may be more complex than currently envisioned.