TY - JOUR T1 - Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0016-14.2015 VL - 2 IS - 2 SP - ENEURO.0016-14.2015 AU - Laleh Sinai AU - Evgueni A. Ivakine AU - Emily Lam AU - Marielle Deurloo AU - Joana Dida AU - Ralph A. Zirngibl AU - Cynthia Jung AU - Jane E. Aubin AU - Zhong-Ping Feng AU - John Yeomans AU - McInnes Roderick R. AU - Lucy R. Osborne AU - John C. Roder Y1 - 2015/03/01 UR - http://www.eneuro.org/content/2/2/ENEURO.0016-14.2015.abstract N2 - Src is a nonreceptor protein tyrosine kinase that is expressed widely throughout the central nervous system and is involved in diverse biological functions. Mice homozygous for a spontaneous mutation in Src (Src thl/thl) exhibited hypersociability and hyperactivity along with impairments in visuospatial, amygdala-dependent, and motor learning as well as an increased startle response to loud tones. The phenotype of Src thl/thl mice showed significant overlap with Williams-Beuren syndrome (WBS), a disorder caused by the deletion of several genes, including General Transcription Factor 2-I (GTF2I). Src phosphorylation regulates the movement of GTF2I protein (TFII-I) between the nucleus, where it is a transcriptional activator, and the cytoplasm, where it regulates trafficking of transient receptor potential cation channel, subfamily C, member 3 (TRPC3) subunits to the plasma membrane. Here, we demonstrate altered cellular localization of both TFII-I and TRPC3 in the Src mutants, suggesting that disruption of Src can phenocopy behavioral phenotypes observed in WBS through its regulation of TFII-I. ER -