mTORC1 is involved in DGKβ-induced neurite outgrowth and spinogenesis
mTORC1 is involved in DGKβ-induced neurite outgrowth and spinogenesis
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DOI：
10.1016/j.neuint.2019.104645
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发表时间：
2020-03-01
影响因子：
4.2
通讯作者：
Shirai, Yasuhito
中科院分区：
文献类型：
--
作者：
Nakai, Hiroko;Tsumagari, Ryosuke;Shirai, Yasuhito
二酰基甘油激酶β (DGK β)是一种将DG转化为磷脂酸（PA）的酶，在神经元中特异性表达，特别是在大脑皮层、海马和纹状体中。我们之前报道过DGK β诱导神经突生长和脊髓发生，促进包括情绪和记忆在内的高级脑功能，并且DGK β通过Cl结构域和c端的一组碱性氨基酸在质膜定位是其功能所必需的。为了阐明DGK β参与神经元发育的机制，我们利用人神经母细胞瘤SH-SY5Y细胞研究了DGK β活性是否诱导神经突生长。DGK β通过激酶依赖途径激活哺乳动物雷帕霉素靶蛋白复合物1 （mTORC1）诱导神经突生长。此外，在原代培养的皮质和海马神经元中，抑制mTORC1可抑制DGK β诱导的神经突生长、分支和脊髓发生。这些结果表明DGK β通过激活激酶依赖途径的mTORC1诱导神经突生长和脊髓发生。
Diacylglycerol kinase beta (DGK beta) is an enzyme converting DG to phosphatidic acid (PA) and is specifically expressed in neurons, especially those in the cerebral cortex, hippocampus and striatum. We previously reported that DGK beta induces neurite outgrowth and spinogenesis, contributing to higher brain function including emotion and memory, and plasma membrane localization of DGK beta via the Cl domain and a cluster of basic amino acids at the C-terminus is necessary for its function. To clarify the mechanisms involved in neuronal development by DGK beta, we investigated whether DGK beta activity induces neurite outgrowth using human neuroblastoma SH-SY5Y cells. DGK beta induced neurite outgrowth by activation of mammalian target of rapamycin complex 1 (mTORC1) through a kinase-dependent pathway. In addition, in primary cultured cortical and hippocampal neurons, inhibition of mTORC1 abolished DGK beta induced-neurite outgrowth, branching and spinogenesis. These results indicated that DGK beta induces neurite outgrowth and spinogenesis by activating mTORC1 in a kinase-dependent pathway.