CONSERVATION OF THE AMINO-ACID-SEQUENCE OF SV2, A TRANSMEMBRANE TRANSPORTER IN SYNAPTIC VESICLES AND ENDOCRINE-CELLS

SV2 is a secretory vesicle-specific protein produced by all neurons and by endocrine cells. The deduced amino acid (aa) sequence of this protein indicates that it is a transmembrane transporter [Bajjalieh et al., Science 257 (1992) 1271-1273; Feany et al., Cell 70 (1992) 861-867; Gingrich et al., FEBS Lett. 312(1992) 115-122]. To determine the regions of the protein that are the most highly conserved throughout evolution, and might therefore be essential for the function of SV2, we isolated a cDNA clone encoding SV2 from the elasmobranch fish, Discopyge ommata, and compared the deduced aa sequence to two isoforms from rat, SV2A and SV2B [Bajjalieh et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2150-2154]. The comparison indicates that although the N-terminal cytoplasmic domain of SV2 is the most divergent region, it contains a highly conserved sequence that is predicted to be the epitope for a monoclonal antibody that crossreacts with all species and two isoforms of SV2 [Buckley and Kelly, J. Cell Biol. 100 (1985) 1284-1294 Baijalieh et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2150-2154]. The remainder of the protein is highly conserved: 62% of the aa in SV2 from D. ommata are identical to the rat SV2A sequence, and 12% are conservative substitutions. The high degree of conservation of this protein throughout evolution and across species indicates that it mediates a critical function of synaptic vesicles.