Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
Liang Zhou,
Chong-Yu Shao,
Ya-Jun Xie,
Na Wang,
Si-Min Xu,
Ben-Yan Luo,
Zhi-Ying Wu,
Yue Hai Ke,
Mengsheng Qiu,
Ying Shen
Affiliations
Liang Zhou
Department of Physiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Brain Science, Guizhou Institution of Higher Education, Zunyi Medical University, Zunyi, China
Chong-Yu Shao
Department of Physiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
Ya-Jun Xie
Department of Physiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
School of Medicine, Zhejiang University City College, Hangzhou, China
Si-Min Xu
Department of Physiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
Ben-Yan Luo
Department of Physiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
Zhi-Ying Wu
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China
Yue Hai Ke
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
Mengsheng Qiu
Institute of Life Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
Department of Physiology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China
Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is downregulated by PDGF stimulation and upregulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3β and regulated its activity, and thereby affects the nuclear accumulation of β-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.
