A 3RD MEMBER OF THE SYNAPSIN GENE FAMILY

Synapsins are a family of neuron specific synaptic vesicle-associated phosphoproteins that have been implicated in synaptogenesis and in the modulation of neurotransmitter release. In mammals, distinct genes fo r synapsins I and II have been identified, each of which gives rise to two alternatively spliced isoforms. We have now cloned and characteri zed a third member of the synapsin gene family, synapsin III, from hum an DNA. Synapsin III gives rise to at least one protein isoform, desig nated synapsin IIIa, in several mammalian species. Synapsin IIIa is as sociated with synaptic vesicles, and its expression appears to be neur on-specific. The primary structure of synapsin IIIa conforms to the do main model previously described for the synapsin family, with domains A, C, and E exhibiting the highest degree of conservation. Synapsin II Ia contains a novel domain, termed domain J, located between domains C and E. The similarities among synapsins I, II, and III in domain orga nization, neuron-specific expression, and subcellular localization sug gest a possible role for synapsin III in the regulation of neurotransm itter release and synaptogenesis. The human synapsin III gene is locat ed on chromosome 22q12-13, which has been identified as a possible sch izophrenia susceptibility locus. On the basis of this localization and the well established neurobiological roles of the synapsins, synapsin III represents a candidate gene for schizophrenia.