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

Abstract

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.

• Authors: Laleh Sinai, Evgueni A Ivakine, Emily Lam, Marielle Deurloo, Joana Dida, Ralph A Zirngibl, Cynthia Jung, Jane E Aubin, Zhong-Ping Feng, John Yeomans, Roderick R McInnes, Lucy R Osborne, John C Roder
• Journal: eNeuro (eNeuro) 2015 Mar-Apr Vol. 2 Issue 2 ISSN: 2373-2822 [Print] United States
• PMID: 26464974 (Publication Type: Journal Article)