Neuroligins were first identified as mammalian postsynaptic cell adhesion molecules that bound specifically to presynaptic membrane proteins called neurexins. There are four neuroligin genes in mammals, and mutations in the human genes encoding neuroligin 3 and neuroligin 4 are associated with autism spectrum disorders (Jamain et al., 2003; Laumonnier et al., 2004; Yan et al., 2005). C. elegans has a single neuroligin gene,
nlg-1 (C40C9.5). Using a transgenic transcriptional reporter, we found that
nlg-1 is expressed in a subset of neurons in C. elegans adults, including ~20 cells in the ventral nerve cord, and ~20 cells in the head. We identified the
nlg-1-expressing cells in the ventral nerve cord as the cholinergic VA and DA motor neurons. The
nlg-1-expressing cells in the head do not fall neatly into a single neuron class or neurotransmitter type, and include the AWA and AWC odorsensory neurons, the AIY, RIA, and URB interneurons, and the RMH and URA motor neurons. We also observe
nlg-1 expression in the midbody PVD mechanosensory and HSN motor neurons, and faint expression in body wall muscles. To examine subcellular localization of the NLG-1 protein, we generated a transgenic NLG-1::YFP fusion protein under the control of the
nlg-1 promoter. We believe that this fusion protein is functional because it rescues all
nlg-1 mutant behaviors (see abstract by Heatherly et al.). We observed NLG-1::YFP fluorescence in neuronal processes, localized chiefly to synaptic regions, especially the nerve ring and the nerve cords. Confocal microscopy revealed that NLG-1::YFP is present at synapses, and is offset from synaptic vesicle and active zone proteins. The C-terminus of the NLG-1 protein contains a Type II PDZ-binding motif which is necessary for proper subcellular localization. We are currently trying to identify the gene products required for proper localization of NLG-1. (Supported by a grant from Autism Speaks).