Differential Regulation of Synaptic Transmission through Tomosyn/Synaptotagmin Interactions in C. elegans

Synaptic transmission is an essential process for neuronal communication in which neurotransmitters are released into the synaptic cleft in response to an action potential, resulting in the activation of postsynaptic receptors. Impairment in this process has been linked to multiple disorders. Thus, investigating the mechanism of neurotransmitter release is important for understanding and developing therapeutics for these diseases. Both tomosyn and synaptotagmin are highly-conserved proteins that are involved in the regulation of neurotransmitter release. While in vitro studies in mammalian cultured neurons demonstrate that tomosyn directly binds to synaptotagmin-1, resulting in inhibition of neurotransmitter release, whether this interaction is maintained in vivo remains to be investigated. The goal of this thesis was to investigate the potential functional interactions of tomosyn with two synaptotagmin isoforms (SNT-1 and SNT-3) that act as a dual calcium sensing system in C. elegans. We demonstrate that TOM-1 differentially interacts with both SNT-1 and SNT-3 to regulate synaptic transmission. Specifically, SNT-1 regulates transport of TOM-1 to synapses, while TOM-1 regulates SNT-3 expression levels. Additional evidence suggests that TOM-1 impacts both SNT-1 and SNT-3 roles in both exocytosis and endocytosis. Together, my work suggests novel differential regulation of synaptic transmission through the interaction of tomosyn with a calcium sensor system.