Autism is a debilitating neurodevelopmental disorder associated with social and cognitive deficits. Autismcompromises the quality of life of affected individuals and place an enormous financial and emotional burdenon families and the healthcare system. Advances that promote novel therapeutic approaches are thus a criticalneed. Mutations in CTNND2, encoding δ-catenin, have been identified in autism. However, the normal functionalroles of δ-catenin and how autism mutations perturb this functional role remain unclear. We have identifiedcritical roles for δ-catenin in regulating dendrites, spines and transcription. Based on our preliminary data, wepropose that δ-catenin interacts with specific interactors in different cellular compartments to function in thesediverse signaling pathways. Further, we propose that autism mutations perturb these interactions or ability tofunction in these signaling pathways, thus compromising neural circuit formation and contributing to thephenotype of autism. In this proposal, we propose to take advantage of an affinity purification technique to identify andcharacterize compartment specific binding partners of δ-catenin from the mouse hippocampus. We expect thatthese studies will aid in further defining the functional roles of δ−catenin and delineate the signaling pathwaysthat are aberrant in autism associated with mutations in CTNND2. Thus these studies will eventually aid thedevelopment of novel therapeutic approaches for this devastating disorder.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
