PNAS
Abstract
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.
| 论文编号: | DOI:10.1073/pnas.1804083115 |
| 论文题目: | cTAGE5/MEA6 Plays a Critical Role in Neuronal Cellular Components Trafficking and Brain Development |
| 英文论文题目: | cTAGE5/MEA6 Plays a Critical Role in Neuronal Cellular Components Trafficking and Brain Development |
| 第一作者: | Feng Zhang, Yaqing Wang, Tao Wang, Li Yao, Sin Man Lam, Xiahe Huang, Junwan Fan, Qin Wang, Liang Liu, Yisheng Jiang, Hongsheng Zhang, Lei Shi, Mei Yu, Guanghou Shui, Yingchun Wang, Fei Gao, Xiaohui Zhang, and Zhiheng Xu |
| 英文第一作者: | Feng Zhang, Yaqing Wang, Tao Wang, Li Yao, Sin Man Lam, Xiahe Huang, Junwan Fan, Qin Wang, Liang Liu, Yisheng Jiang, Hongsheng Zhang, Lei Shi, Mei Yu, Guanghou Shui, Yingchun Wang, Fei Gao, Xiaohui Zhang, and Zhiheng Xu |
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| 发表年度: | 2018-09-21 |
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| 摘要: | 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. |
| 英文摘要: | 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. |
| 刊物名称: | PNAS |
| 英文刊物名称: | PNAS |
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| 其它备注: | Feng Zhang, Yaqing Wang, Tao Wang, Li Yao, Sin Man Lam, Xiahe Huang, Junwan Fan, Qin Wang, Liang Liu, Yisheng Jiang, Hongsheng Zhang, Lei Shi, Mei Yu, Guanghou Shui, Yingchun Wang, Fei Gao, Xiaohui Zhang, and Zhiheng Xu. cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development. PNAS. DOI:10.1073/pnas.1804083115 |
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