cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development

Zhang Feng; Wang Yaqing; Wang TaoYao LiLam Sin ManHuang XiaheFan JunwanWang QinLiu LiangJiang YishengZhang HongshengShi LeiYu MeiShui GuanghouWang YingchunGao FeiZhang XiaohuiXu Zhiheng

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cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development

机译：cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development

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Normal neural development is essential for the formation of neuronal networks and brain function. Cutaneous T cell lymphoma-associated antigen 5 (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the secretion of proteins. However, its roles in the transport of nonsecretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is important for brain development and function. Conditional knockout of cTAGE5/MEA6 in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, spine formation and maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAM and SEC23, leading to persistent activation of SAM and defects in COPII vesicle formation and transport from the endoplasmic reticulum to the Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines but also the signaling pathways required for neuronal development. Because mutations in cTAGE5/MEA6 have been found in patients with Fahr's disease, our study potentially also provides insight into the pathogenesis of this disorder.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2018年第40期|E9449-E9458|共10页
作者
Zhang Feng; Wang Yaqing; Wang TaoYao LiLam Sin ManHuang XiaheFan JunwanWang QinLiu LiangJiang YishengZhang HongshengShi LeiYu MeiShui GuanghouWang YingchunGao FeiZhang XiaohuiXu Zhiheng;
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作者单位

Chinese Acad Sci, Inst Genet & Dev Biol, Ctr Excellence Brain Sci & Intelligence Technol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China;

Beijing Normal Univ, IDG McGovern Inst Brain Res, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China;

Chinese Acad Sci, State Key Lab Reprod Biol, Inst Zool, Beijing 100101, Peoples R China;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
cTAGE5; MEA6; brain development; COPII; vesicle trafficking;

cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development

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