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Src 的破坏与威廉姆斯-贝伦综合征相关表型有关，并改变了 TFII-I 的细胞定位。

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

机构信息

Institute of Medical Science, University of Toronto , Toronto, Ontario, M5S 1A8, Canada ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto Ontario, M5S 3E1, Canada.

Programs in Genomics and Developmental Biology, The Hospital for Sick Children Research Institute, Peter Gilgan Center for Research and Learning , Toronto, Ontario, M5G 0A4, Canada.

出版信息

eNeuro. 2015 Mar 30;2(2). doi: 10.1523/ENEURO.0016-14.2015. eCollection 2015 Mar-Apr.

DOI:10.1523/ENEURO.0016-14.2015
PMID:26464974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4596087/
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.

摘要

Src 是一种非受体蛋白酪氨酸激酶，广泛表达于中枢神经系统，参与多种生物学功能。Src（thl/thl）突变的纯合子小鼠表现出过度社交和过度活跃，同时伴有视空间、杏仁核依赖和运动学习障碍，以及对大声响的惊跳反应增加。Src（thl/thl）小鼠的表型与威廉姆斯-贝伦综合征（WBS）有显著重叠，WBS 是一种由包括一般转录因子 2-I（GTF2I）在内的多个基因缺失引起的疾病。Src 磷酸化调节 GTF2I 蛋白（TFII-I）在核内（作为转录激活因子）和细胞质（调节瞬时受体电位阳离子通道亚家族 C，成员 3（TRPC3）亚基向质膜的运输）之间的运动。在这里，我们证明了 Src 突变体中 TFII-I 和 TRPC3 的细胞定位都发生了改变，这表明 Src 的破坏可以通过其对 TFII-I 的调节来模拟 WBS 中观察到的行为表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/fcba33642459/enu0021500630010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/8e5ecc0b5c0b/enu0021500630001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/40536d586c85/enu0021500630002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/5bb2ace42266/enu0021500630003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/21f77c30f365/enu0021500630004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/fcff901d9ca8/enu0021500630005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/12a234e847b8/enu0021500630006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/e3e55ecb0825/enu0021500630007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/09981b500ce6/enu0021500630008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/9514da7db86e/enu0021500630009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/fcba33642459/enu0021500630010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/8e5ecc0b5c0b/enu0021500630001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/40536d586c85/enu0021500630002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/5bb2ace42266/enu0021500630003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/21f77c30f365/enu0021500630004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/fcff901d9ca8/enu0021500630005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/12a234e847b8/enu0021500630006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/e3e55ecb0825/enu0021500630007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/09981b500ce6/enu0021500630008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/9514da7db86e/enu0021500630009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b8c/4596087/fcba33642459/enu0021500630010.jpg

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