Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling
Zhixiong Liu, … , Zhanxiang Wang, Liang Zhang
Zhixiong Liu, … , Zhanxiang Wang, Liang Zhang
Published February 10, 2022
Citation Information: J Clin Invest. 2022;132(7):e155096. https://doi.org/10.1172/JCI155096.
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Research Article Cell biology Neuroscience

Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling

Abstract

Dysfunction of protein trafficking has been intensively associated with neurological diseases, including neurodegeneration, but whether and how protein transport contributes to oligodendrocyte (OL) maturation and myelin repair in white matter injury remains unclear. ER-to-Golgi trafficking of newly synthesized proteins is mediated by coat protein complex II (COPII). Here, we demonstrate that the COPII component Sec13 was essential for OL differentiation and postnatal myelination. Ablation of Sec13 in the OL lineage prevented OPC differentiation and inhibited myelination and remyelination after demyelinating injury in the central nervous system (CNS), while improving protein trafficking by tauroursodeoxycholic acid (TUDCA) or ectopic expression of COPII components accelerated myelination. COPII components were upregulated in OL lineage cells after demyelinating injury. Loss of Sec13 altered the secretome of OLs and inhibited the secretion of pleiotrophin (PTN), which was found to function as an autocrine factor to promote OL differentiation and myelin repair. These data suggest that Sec13-dependent protein transport is essential for OL differentiation and that Sec13-mediated PTN autocrine signaling is required for proper myelination and remyelination.

Authors

Zhixiong Liu, Minbiao Yan, Wanying Lei, Rencai Jiang, Wenxiu Dai, Jialin Chen, Chaomeng Wang, Li Li, Mei Wu, Ximing Nian, Daopeng Li, Di Sun, Xiaoqi Lv, Chaoying Wang, Changchuan Xie, Luming Yao, Caiming Wu, Jin Hu, Naian Xiao, Wei Mo, Zhanxiang Wang, Liang Zhang

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