Understanding synaptic function and RNA splicing using C elegans as a model system

Abstract

Locomotion in C. elegans serves as the read out of diverse behavioral studies. The sinusoidal newlinemovement of C. elegans is the output of an intricate balance between the contraction and relaxation newlineof contralateral muscles. The nicotinic acetylcholine receptors are expressed in neural circuits that newlinecontrol movement and hence act as key players in maintaining the movement of worms. Diverse newlinemolecular pathways regulate these receptors. The use of pharmacological assays has helped in newlineunraveling the vast number of genes involved in signaling across the synapses. Using newlinepharmacological assays we have identified a gene that is required for maintaining subtype specific newlinenicotinic acetylcholine receptors (AChRs) at the synapse in C. elegans. HPO-30 encodes a conserved newlinetetra span membrane protein that belongs to the claudin superfamily of proteins. In the absence of newlinehpo-30, a subset of AChRs present in the body wall muscles decreases at the neuromuscular junction newline(NMJ). However, the hpo-30 mutant does not affect the other subtype of AChRs or GABA receptors newlineexpressed on the body wall muscle cells. The HPO-30 protein localizes at the NMJ and shows genetic newlineand physical interaction with AChRs. Using genetic and electrophysiological assays we have newlinedemonstrated that HPO-30 functions through NLG-1 at the NMJ to maintain the postsynaptic receptor newlinelevels. Taken together, this work suggests a novel function for a tight junction protein in maintaining newlinenormal receptor levels at the NMJ. newline