Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses

Zhan, Jiangshan1,2; Gao, Yuanxu3; Heinig, Leo2; Beecken, Malena2; Huo, Yangbo1; Zhang, Wansong4; Wang, Pingzhang1; Wei, Tianzi4; Tian, Ruilin4; Han, Wenling1; Yu, Albert Cheung Hoi1; Kipp, Markus2; Kaddatz, Hannes2,5

2023-08-01

10.3390/cells12162085

CELLS   影响因子和分区

2073-4409

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 Cmtm5 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 Atf4 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 Cmtm5 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.

CMTM5 multiple sclerosis cuprizone experimental autoimmune encephalomyelitis demyelination endoplasmic reticulum stress

SCI

英语

其他

Cell Biology

Cell Biology

WOS:001056487600001

MDPI

Web of Science

1.Peking Univ Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100191, Peoples R China
2.Rostock Univ, Inst Anat, Med Ctr, Gertrudenstr 9, D-18057 Rostock, Germany
3.Macau Univ Sci & Technol, Fac Med, Ctr Biomed & Innovat, Taipa 999078, Macao, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Dept Med Neurosci, Shenzhen 518055, Peoples R China
5.Univ Rostock, Univ Med Ctr Rostock, Dept Neurol, D-18057 Rostock, Germany

Zhan, Jiangshan,Gao, Yuanxu,Heinig, Leo,et al. Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses[J]. CELLS,2023,12(16).

Zhan, Jiangshan.,Gao, Yuanxu.,Heinig, Leo.,Beecken, Malena.,Huo, Yangbo.,...&Kaddatz, Hannes.(2023).Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses.CELLS,12(16).

Zhan, Jiangshan,et al."Loss of the Novel Myelin Protein CMTM5 in Multiple Sclerosis Lesions and Its Involvement in Oligodendroglial Stress Responses".CELLS 12.16(2023).