Molecular Mechanisms Regulating Calcium-Dependent Release at C. elegans Synapses

Efficient release of neurotransmitters is critical for information exchange between neurons and their targets. This process is highly conserved and requires the coordinated function of many proteins: UNC-10/RIM (Rab3-interacting molecule) forms a complex with Rab3 on vesicles and UNC-13/MUNC-13 at release sites to position vesicles for priming. Upon Ca2+ influx, integral vesicle Ca2+-sensors named synaptotagmins (Syts) associate with the SNARE complex to facilitate fusion of docked vesicles and neurotransmitter release. Functional interactions of these and other proteins that function at the site of release are being further characterized to better understand the process by which synapse function is regulated. This thesis includes new ultrastructural, functional and genetic analyses that contribute to the understanding of how synaptotagmins and active zone proteins regulate synaptic release.