State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Zhongshan Hospital, Fudan University, Shanghai, China.
Glia. 2022 Feb;70(2):379-392. doi: 10.1002/glia.24113. Epub 2021 Nov 1.
Myelin sheath is an important structure to maintain functions of the nerves in central nervous system. Protein palmitoylation has been established as a sorting determinant for the transport of myelin-forming proteins to the myelin membrane, however, its function in the regulation of oligodendrocyte development remains unknown. Here, we show that an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC5, is involved in the control of oligodendrocyte development. Loss of Zdhhc5 in oligodendrocytes inhibits myelination and remyelination by reducing total myelinating oligodendrocyte population. STAT3 is the primary substrate for DHHC5 palmitoylation in oligodendrocytes. Zdhhc5 ablation reduces STAT3 palmitoylation and suppresses STAT3 phosphorylation and activation. As a result, the transcription of the myelin-related and anti-apoptosis genes is inhibited, leading to suppressed oligodendrocyte development and myelination. Our findings demonstrate a key role DHHC5 in controlling myelinogenesis.
髓鞘是维持中枢神经系统神经功能的重要结构。蛋白质棕榈酰化已被确定为将髓鞘形成蛋白运输到髓鞘膜的分选决定因素，然而，其在调控少突胶质细胞发育中的作用尚不清楚。在这里，我们表明，含有 DHHC 基序的棕榈酰基转移酶 DHHC5 参与了少突胶质细胞的发育调控。少突胶质细胞中 Zdhhc5 的缺失通过减少总髓鞘形成少突胶质细胞群体来抑制髓鞘形成和再髓鞘化。STAT3 是少突胶质细胞中 DHHC5 棕榈酰化的主要底物。Zdhhc5 缺失会减少 STAT3 棕榈酰化并抑制 STAT3 磷酸化和激活。结果，与髓鞘相关和抗细胞凋亡的基因的转录受到抑制，导致少突胶质细胞发育和髓鞘形成受到抑制。我们的研究结果表明，DHHC5 在控制髓鞘发生中起着关键作用。
