Isolation and characterization of peptides derived from the cleavage of the cytoplasmic domain of synaptophysin in frog brain.

Three overlapping peptides have been isolated from the whole brain of the European green frog, Rana ridibunda and identified as fragments of the cytoplasmic domain of the synaptic vesicle membrane protein, synaptophysin. The primary structures of the peptides define the amino acid sequence of the 58 residues at the COOH-terminus of the protein and indicate that fragments arose from proteolytic cleavages at the COOH-terminal side of aspartyl residues. The overall conservation of structure of the cytoplasmic domain between the mammalian and amphibian proteins is relatively poor (58% sequence identity between frog and rat synaptophysin). However, the pattern of repeating tyrosine residues that is present in mammalian and Torpedo synaptophysins is also found in the frog protein suggesting that this structural motif is necessary for the, as yet unknown, function of the protein. The cytoplasmic region of frog synaptophysin is also rich in glutamine and glycine residues, but the putative consensus repeating sequence Tyr-Gly-Pro/Gln-Gln-Gly in mammalian synaptophysins does not occur in the frog protein. The data raise the possibility that synaptophysin, like the chromogranins and secretogranin II, may function as the precursor of biologically active peptides.