OVEREXPRESSION OF SYNAPTOPHYSIN ENHANCES NEUROTRANSMITTER SECRETION AT XENOPUS NEUROMUSCULAR SYNAPSES

Previous studies have suggested the importance of synaptophysin (p38), a major integral membrane protein of the synaptic vesicle, in transmi tter secretion, but few have directly addressed its functional role at intact synapses. In the present study, injection of synthetic mRNA fo r synaptophysin into one of the early blastomeres of a Xenopus embryo resulted in elevated synaptophysin expression in 1 and 2 d embryos and . in cultured spinal neurons derived from the injected blastomere, as shown by immunocytochemistry. At neuromuscular synapses made by neuron s overexpressing synaptophysin [p38(+)] in 1 d cell cultures, the spon taneous synaptic currents (SSCs) showed a markedly higher frequency, a s compared to control synapses. This increase in frequency was not acc ompanied by a change in the mean amplitude or the amplitude distributi on of the SSCs, suggesting that synaptophysin is not involved in deter mining the size of transmitter quanta. The impulse-evoked synaptic cur rents (ESCs) of synapses made by p38(+) neurons showed increased ampli tude as well as reduced fluctuation and delay of onset of ESCs. Under high-frequency tetanic stimulation at 5 Hz, the rate of tetanus-induce d depression was faster for p38(+) neurons. Taken together, these resu lts suggest a role for synaptophysin in the late steps of transmitter secretion, affecting the probability of vesicular exocytosis and/or th e number of synaptic vesicles initially docked at the active zone.