Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I

• Published in: eNeuro 2015-03, Vol.2 (2), p.ENEURO.0016-14.2015
• Main Authors: Sinai, Laleh, Ivakine, Evgueni A, Lam, Emily, Deurloo, Marielle, Dida, Joana, Zirngibl, Ralph A, Jung, Cynthia, Aubin, Jane E, Feng, Zhong-Ping, Yeomans, John, McInnes, Roderick R, Osborne, Lucy R, Roder, John C
• Format: Article
• Language: English
• ISSN: 2373-2822; 2373-2822
• DOI: 10.1523/ENEURO.0016-14.2015

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.