Over 30 distinct genes have been identified as either causing or contributing to the cause of autism. To better understand how such a diverse array of genes can cause similar ASD phenotypes, a search was conducted for the binding partners of proteins encoded by autism-associated genes and an autism protein interaction network (an "interactome") was developed that contains over 900 protein interactions. This interactome revealed three "hub" proteins that are centers for interaction: FXR1 (related to Fragile X Mental Retardation Protein), SHANK3, and TSC1 (implicated in tuberous sclerosis). Moreover, SHANK3 interacts with two distinct classes of proteins: one involved in synapse structure, the other involved in RNA metabolism and translation. To gain insight into key mechanisms underlying ASD pathogenesis, this research will identify and characterize the native SHANK3 complexes at the synapse using a mouse model. Detailed behavioral and biochemical studies will establish a functional relationship between SHANK3 and FXR proteins and provide a foundation for detailed mechanistic studies that should benefit a broad population of ASD patients.