Components within the synaptic vesicle membrane associate with plasma membrane proteins at sites of transmitter release where they are thought to promote membrane fusion. One central player in this process is the plasma membrane protein syntaxin, in C. elegans encoded by unc-64. The null mutant arrests at the L1 stage and exhibits little discernible movement.
Hypomorphic alleles are paralyzed and aldicarb-resistant, yet otherwise healthy in appearance.
Although the rate of pharyngeal pumping is normal, electrophysiological analysis reveals abnormal synaptic function. The progressive increase of M3 amplitudes within a pump suggests that repetitive firing may relieve the defect, possibly by raising intracellular calcium levels. This is consistent with the observation that syntaxin associates with and modifies the properties of N-type calcium channels found at the nerve terminal. We are in the process of testing whether the reduced transmitter release in unc-64 is due to defective calcium entry by varying extracellular calcium in dissected pharynxes. We now have genetic evidence revealing in vivo importance of the syntaxin-synaptobrevin interaction to synaptic transmission.