Functional analysis of novel proteins associated with nicotinic acetylcholine receptors and synaptic vesicles in Caenorhabditis elegans

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Chemical synapses are contact sites between neurons and thus central for information transfer in the nervous system. At the pre-synaptic side, a complex protein machinery mediates release of neurotransmitters (stored in synaptic vesicles - SVs), and the downstream cell is activated by a post-synaptic apparatus containing specific neurotransmitter receptors. By purification, we identified proteins associated with post-synaptic nicotinic acetylcholine receptors (nAChRs) in the nematode Caenorhabditis elegans. As we showed by methods including electrophysiology, three of these nicotinic receptor associated proteins, NRA-1, -2 and -3, regulate synaptic density or functional properties of nAChRs. Function of these proteins shall now be characterized in detail. Similarly, via purification and cross-species conservation, we identify novel C. elegans proteins as part of SVs. These proteins are functionally characterized in (mutant) animals lacking them, by pharmacological, behavioural and cell biological assays, electrophysiology, and a new tool we developed for exogenous photo-stimulation of neural activity, the light-gated cation channel Channelrhodopsin-2 (ChR2). Specifically, we want to further develop ChR2 for the analysis of defects in synaptic transmission at the neuromuscular synapse.