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Ermin is a p116 RIP ‐interacting protein promoting oligodendroglial differentiation and myelin maintenance
Author(s) -
Wang Shan,
Wang Tao,
Liu Tao,
Xie RouGang,
Zhao XiangHui,
Wang Lei,
Yang Qian,
Jia LinTao,
Han Jing
Publication year - 2020
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23838
Subject(s) - myelin , oligodendrocyte , biology , microbiology and biotechnology , rhoa , cytoskeleton , remyelination , knockout mouse , neuroscience , central nervous system , signal transduction , biochemistry , cell , gene
Myelin sheaths, which insulate the axons and ensure saltatory conduction of the nerve impulse, are generated and maintained via largely uncharacterized mechanisms. Ermin is an oligodendrocyte‐specific protein associated with the cytoskeleton, but how it regulates cytoskeletal remodeling during oligodendrocyte differentiation and its role in myelin maintenance are not clear. To address this, we generated mice constitutively deficient for Ermn , the Ermin‐coding gene. We found that aged Ermn ‐knockout mice exhibit an aberrant myelin architecture, with splitting of myelin layers, peeling of the myelin sheath from axons, and breakdown of myelinated fibers. As a result, these mice had remarkably impaired motor coordination. Ermn knockout also accelerated cuprizone‐induced demyelination and exacerbated the associated movement disorders. Ermin was found to contribute to oligodendrocyte morphogenesis by associating with the myosin phosphatase Rho interacting protein (Mprip/p116 RIP ) and inactivating RhoA, a GTPase that controls cytoskeletal rearrangement in differentiating cells. These findings provide novel insights into the mechanisms regulating oligodendroglial differentiation, the maintenance of the myelin sheaths, and remyelination.