Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses
This study comprehensively addresses the involvement of the protein CKLF-like Marvel transmembrane domain-containing family member 5 (CMTM5) in the context of demyelination and cytodegenerative autoimmune diseases, particularly multiple Sclerosis (MS). An observed reduction in CMTM5 expression in po...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2085 |
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| author | Jiangshan Zhan Yuanxu Gao Leo Heinig Malena Beecken Yangbo Huo Wansong Zhang Pingzhang Wang Tianzi Wei Ruilin Tian Wenling Han Albert Cheung Hoi Yu Markus Kipp Hannes Kaddatz |
| author_facet | Jiangshan Zhan Yuanxu Gao Leo Heinig Malena Beecken Yangbo Huo Wansong Zhang Pingzhang Wang Tianzi Wei Ruilin Tian Wenling Han Albert Cheung Hoi Yu Markus Kipp Hannes Kaddatz |
| author_sort | Jiangshan Zhan |
| collection | DOAJ |
| description | This study comprehensively addresses the involvement of the protein CKLF-like Marvel transmembrane domain-containing family member 5 (CMTM5) in the context of demyelination and cytodegenerative autoimmune diseases, particularly multiple Sclerosis (MS). An observed reduction in CMTM5 expression in post-mortem MS lesions prompted further investigations in both in vitro and in vivo animal models. In the cuprizone animal model, we detected a decrease in CMTM5 expression in oligodendrocytes that is absent in other members of the CMTM protein family. Our findings also confirm these results in the experimental autoimmune encephalomyelitis (EAE) model with decreased CMTM5 expression in both cerebellum and spinal cord white matter. We also examined the effects of a <i>Cmtm5</i> knockdown in vitro in the oligodendroglial Oli-neu mouse cell line using the CRISPR interference technique. Interestingly, we found no effects on cell response to thapsigargin-induced endoplasmic reticulum (ER) stress as determined by <i>Atf4</i> activity, an indicator of cellular stress responses. Overall, these results substantiate previous findings suggesting that CMTM5, rather than contributing to myelin biogenesis, is involved in maintaining axonal integrity. Our study further demonstrates that the knockdown of <i>Cmtm5</i> in vitro does not modulate oligodendroglial responses to ER stress. These results warrant further investigation into the functional role of CMTM5 during axonal degeneration in the context of demyelinating conditions. |
| first_indexed | 2024-03-11T00:02:02Z |
| format | Article |
| id | doaj.art-26b225ec0a85468b9a068f6ffeb55654 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:02:02Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-26b225ec0a85468b9a068f6ffeb556542023-11-19T00:37:16ZengMDPI AGCells2073-44092023-08-011216208510.3390/cells12162085Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress ResponsesJiangshan Zhan0Yuanxu Gao1Leo Heinig2Malena Beecken3Yangbo Huo4Wansong Zhang5Pingzhang Wang6Tianzi Wei7Ruilin Tian8Wenling Han9Albert Cheung Hoi Yu10Markus Kipp11Hannes Kaddatz12School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaCenter for Biomedicine and Innovations, Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau 999078, ChinaInstitute of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, GermanyInstitute of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, GermanySchool of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Medical Neuroscience, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaSchool of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Medical Neuroscience, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Medical Neuroscience, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaSchool of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaSchool of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaInstitute of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, GermanyInstitute of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, GermanyThis study comprehensively addresses the involvement of the protein CKLF-like Marvel transmembrane domain-containing family member 5 (CMTM5) in the context of demyelination and cytodegenerative autoimmune diseases, particularly multiple Sclerosis (MS). An observed reduction in CMTM5 expression in post-mortem MS lesions prompted further investigations in both in vitro and in vivo animal models. In the cuprizone animal model, we detected a decrease in CMTM5 expression in oligodendrocytes that is absent in other members of the CMTM protein family. Our findings also confirm these results in the experimental autoimmune encephalomyelitis (EAE) model with decreased CMTM5 expression in both cerebellum and spinal cord white matter. We also examined the effects of a <i>Cmtm5</i> knockdown in vitro in the oligodendroglial Oli-neu mouse cell line using the CRISPR interference technique. Interestingly, we found no effects on cell response to thapsigargin-induced endoplasmic reticulum (ER) stress as determined by <i>Atf4</i> activity, an indicator of cellular stress responses. Overall, these results substantiate previous findings suggesting that CMTM5, rather than contributing to myelin biogenesis, is involved in maintaining axonal integrity. Our study further demonstrates that the knockdown of <i>Cmtm5</i> in vitro does not modulate oligodendroglial responses to ER stress. These results warrant further investigation into the functional role of CMTM5 during axonal degeneration in the context of demyelinating conditions.https://www.mdpi.com/2073-4409/12/16/2085CMTM5multiple sclerosiscuprizoneexperimental autoimmune encephalomyelitisdemyelinationendoplasmic reticulum stress |
| spellingShingle | Jiangshan Zhan Yuanxu Gao Leo Heinig Malena Beecken Yangbo Huo Wansong Zhang Pingzhang Wang Tianzi Wei Ruilin Tian Wenling Han Albert Cheung Hoi Yu Markus Kipp Hannes Kaddatz Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses Cells CMTM5 multiple sclerosis cuprizone experimental autoimmune encephalomyelitis demyelination endoplasmic reticulum stress |
| title | Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses |
| title_full | Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses |
| title_fullStr | Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses |
| title_full_unstemmed | Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses |
| title_short | Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses |
| title_sort | loss of the novel myelin protein cmtm5 in multiple sclerosis lesions and its involvement in oligodendroglial stress responses |
| topic | CMTM5 multiple sclerosis cuprizone experimental autoimmune encephalomyelitis demyelination endoplasmic reticulum stress |
| url | https://www.mdpi.com/2073-4409/12/16/2085 |
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