cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development.
cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development.
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cTAGE5/MEA6 在神经元细胞成分运输和大脑发育中发挥着关键作用。
DOI：
10.1073/pnas.1804083115
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发表时间：
2018
影响因子：
11.1
通讯作者：
Xu Zhiheng
中科院分区：
文献类型：
--
作者：
Zhang Feng;Wang Yaqing;Wang Tao;Yao Li;Lam Sin Man;Huang Xiahe;Fan Junwan;Wang Qin;Liu Liang;Jiang Yisheng;Zhang Hongsheng;Shi Lei;Yu Mei;Shui Guanghou;Wang Yingchun;Gao Fei;Zhang Xiaohui;Xu Zhiheng
正常的神经发育对神经元网络的形成和大脑功能是必不可少的。皮肤T细胞淋巴瘤相关抗原5(CTAGE5)/脑膜瘤表达抗原6(MEA6)在蛋白质的分泌中起着关键作用。然而，它在非分泌性细胞成分的运输和脑发育中的作用仍不清楚。在这里，我们展示了cTAGE5/MEA6对大脑发育和功能的重要作用。大脑中cTAGE5/MEA6的条件性基因敲除会导致严重的神经发育缺陷，包括树突生长和分支、脊柱形成和维持、星形胶质细胞激活和异常行为的缺陷。我们发现，cTAGE5/MEA6的丢失影响了外壳蛋白复合体II(COPII)成分SAR1和SEC23之间的相互作用，导致SAR1的持续激活和COPII囊泡形成和从内质网到高尔基体的运输缺陷，以及神经元中膜成分的运输受到干扰。这些缺陷不仅影响树突和棘突发育所需物质的运输，还影响神经元发育所需的信号通路。由于在Fahr病患者中发现了cTAGE5/MEA6突变，我们的研究也可能为这种疾病的发病机制提供洞察力。
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 ofcTAGE5/MEA6in 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, SAR1 and SEC23, leading to persistent activation of SAR1 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.