Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
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 ta...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52056 |
| _version_ | 1811236801787985920 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Liang Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:14:21Z |
| format | Article |
| id | doaj.art-441fa9d3f87a4bed8cdbb5c049edca3a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:14:21Z |
| publishDate | 2020-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-441fa9d3f87a4bed8cdbb5c049edca3a2022-12-22T03:33:28ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.52056Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelinationLiang Zhou0Chong-Yu Shao1Ya-Jun Xie2Na Wang3https://orcid.org/0000-0002-1438-1508Si-Min Xu4Ben-Yan Luo5Zhi-Ying Wu6Yue Hai Ke7Mengsheng Qiu8Ying Shen9https://orcid.org/0000-0001-7034-5328Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaSchool of Medicine, Zhejiang University City College, Hangzhou, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Life Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, ChinaDepartment 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, ChinaOligodendrocytes (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.https://elifesciences.org/articles/52056oligodendrocytemyelinGab1PDGFGSK3β |
| spellingShingle | 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 Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination eLife oligodendrocyte myelin Gab1 PDGF GSK3β |
| title | Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination |
| title_full | Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination |
| title_fullStr | Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination |
| title_full_unstemmed | Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination |
| title_short | Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination |
| title_sort | gab1 mediates pdgf signaling and is essential to oligodendrocyte differentiation and cns myelination |
| topic | oligodendrocyte myelin Gab1 PDGF GSK3β |
| url | https://elifesciences.org/articles/52056 |
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