Genetic analysis of neurotransmitter release at the synapse

The recent application of genetics to the study of synaptic mechanisms has examined the in vivo significance of individual synaptic proteins and has tested hypotheses that were derived from biochemical observations on these proteins. In the case of synapsin I and Rab3A, the phenotypes of mice lacking these proteins was startlingly mild; only subtle alterations in transmission were observed. Whereas in synaptotagmin mutants of flies and nematodes, transmission was severely curtailed, though not abolished. A detailed analysis of the phenotype has led to a hypothesis that this protein stabilizes the docking of vesicles at release sites. The analysis of additional synaptic proteins, Unc-18/Rop and the cysteine string protein, has indicated that these are important players in synaptic mechanisms and may soon illuminate their function at the synapse.