Role of Neuroligin in Synapse Stability
Oklahoma Medical Research Foundation
Basic & Clinical
One of the most important results emerging from the intensive international effort to identify "autism-related" genes has been the demonstration of an association with autism (in some families) of mutations in genes encoding a family of proteins called neuroligins. Neuroligins are synaptic proteins present on post-synaptic cell membranes, and they bind specifically to a set of presynaptic membrane proteins called neurexins. Studies have shown that the binding of neuroligin to neurexin can be sufficient to mediate the assembly of the presynaptic components of a synapse. Mutations disrupting the NLGN3 and NLGN4 genes seem to be associated with autism. The association of autism with a disruption in components involved in synapse structure provides a point of entry for investigating the altered development and "miswiring" of the brain in autistic individuals. This proposal will analyze the molecular genetics and cell biology of neuroligin and its role in synapse maintenance in the nematode C. elegans. Using this simple model system, the researchers will be addressing basic issues about the function of neuroligin in the development of the nervous system. Specifically they will study how synapses are impacted by the absence of neuroligin, what other molecules function with neuroligin to regulate synapse stability, and whether adding back neuroligin to the adult organism can rescue the abnormal development which occurred in its absence. What this means for people with autism: Understanding the function of neuroligin in better detail will reveal the molecular pathways that are disrupted in autism and provide the information needed to design strategies to remediate the biological underpinnings of autism.