Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.
Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.
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DOI：
10.1371/journal.pbio.3001051
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发表时间：
2020-12
期刊：
影响因子：
9.8
通讯作者：
Yan D
中科院分区：
文献类型：
--
作者：
Zhang A;Guan Z;Ockerman K;Dong P;Guo J;Wang Z;Yan D
细胞生长的协调对于大脑的发育是必不可少的，但是对神经胶质和神经元大小调节的分子机制知之甚少。为了研究胶质细胞大小调控的机制，我们使用秀丽隐杆线虫两栖鞘（AMSH）胶质细胞作为模型，并显示保守的顺式高尔基体膜蛋白EAS-1/GOLT 1B负调控胶质细胞的生长。我们发现，eas-1抑制了保守的E3泛素连接酶rnf-145/RNF 145，这反过来又促进了sbp-1/ SREBP的核活化，这是固醇和脂肪酸合成的关键调节因子，从而限制了细胞生长。在早期发育阶段，顺式高尔基体网络中的rnf-145抑制sbp-1的激活以促进胶质细胞的生长，当动物达到成年阶段时，这种抑制通过rnf-145从顺式高尔基体到反式高尔基体网络的eas-1依赖性穿梭而释放，以停止胶质细胞的生长。此外，我们确定了长链多不饱和脂肪酸（LC-PUFA），特别是二十碳五烯酸（EPA），作为eas-1-rnf-145-sbp-1途径的下游产物，其功能是防止神经胶质细胞过度生长。总之，我们的研究结果揭示了一种新的和潜在的保守的神经胶质细胞大小控制机制。神经胶质和神经元大小调节的分子机制知之甚少。在线虫中的这项研究揭示了二十碳五烯酸作为一种途径的下游产物，其功能是防止神经胶质过度生长，这表明神经胶质大小控制的一种新的和潜在的保守机制。
Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth. At early developmental stages, rnf-145 in the cis-Golgi network inhibits sbp-1 activation to promote the growth of glia, and when animals reach the adult stage, this inhibition is released through an eas-1-dependent shuttling of rnf-145 from the cis-Golgi to the trans-Golgi network to stop glial growth. Furthermore, we identified long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA), as downstream products of the eas-1-rnf-145-sbp-1 pathway that functions to prevent the overgrowth of glia. Together, our findings reveal a novel and potentially conserved mechanism underlying glial size control. The molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. This study in nematodes reveals eicosapentaenoic acid as the downstream product of a pathway that functions to prevent the overgrowth of glia, suggesting a novel and potentially conserved mechanism underlying glial size control.
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