Synaptophysin. A widespread constituent of small neuroendocrine vesicles and a new tool in tumor diagnosis.

Synaptophysin, a vesicular integral membrane protein, is specifically expressed in neuroendocrine tissues. According to cDNA cloning studies, it has a molecular weight of 33,300 Dalton, one potential N-glycosylation site at the vesicle inside, four major hydrophobic domains as well as a C-terminus containing approximately 90 amino acids. The C- and N-termini of synaptophysin are located on the cytoplasmic side of the vesicle membrane. No signal sequence is found. Transfection of non-neuroendocrine cells with synaptophysin cDNA leads to the synthesis of synaptophysin-containing vesicles, which contain this protein in highly enriched form and have biophysical properties similar to presynaptic vesicles of neurons. So far, the vesicular content has only been determined in rat neurons, where classical neurotransmitters such as biogenic amines and transmitter-active amino acids were found. Reconstitution of the purified protein in liposomes suggests a possible channel function of synaptophysin. Using mono- and polyvalent antibodies against synaptophysin, a considerable number of studies in several laboratories have shown that this protein is a reliable marker molecule for neuroendocrine tumors of various degrees of differentiation.