PT  - JOURNAL ARTICLE
AU  - Sinai, Laleh
AU  - Ivakine, Evgueni A.
AU  - Lam, Emily
AU  - Deurloo, Marielle
AU  - Dida, Joana
AU  - Zirngibl, Ralph A.
AU  - Jung, Cynthia
AU  - Aubin, Jane E.
AU  - Feng, Zhong-Ping
AU  - Yeomans, John
AU  - Roderick R., McInnes
AU  - Osborne, Lucy R.
AU  - Roder, John C.
TI  - Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I
AID  - 10.1523/ENEURO.0016-14.2015
DP  - 2015 Mar 01
TA  - eneuro
PG  - ENEURO.0016-14.2015
VI  - 2
IP  - 2
4099  - http://www.eneuro.org/content/2/2/ENEURO.0016-14.2015.short
4100  - http://www.eneuro.org/content/2/2/ENEURO.0016-14.2015.full
SO  - eneuro2015 Mar 01; 2
AB  - 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.