Ral GTPases are critical regulators of spinal cord myelination and homeostasis.

Autor:	DeGeer J; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Datwyler AL; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Rickenbach C; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Ommer A; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Gerber D; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Fimiani C; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Gerber J; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Pereira JA; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland., Suter U; Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland. Electronic address: usuter@cell.biol.ethz.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Sep 27; Vol. 40 (13), pp. 111413.
DOI:	10.1016/j.celrep.2022.111413
Abstrakt:	Efficient myelination supports nerve conduction and axonal health throughout life. In the central nervous system, oligodendrocytes (OLs) carry out this demanding anabolic duty in part through biosynthetic pathways controlled by mTOR. We identify Ral GTPases as critical regulators of mouse spinal cord myelination and myelin maintenance. Ablation of Ral GTPases (RalA, RalB) in OL-lineage cells impairs timely onset and radial growth of developmental myelination, accompanied by increased endosomal/lysosomal abundance. Further examinations, including transcriptomic analyses of Ral-deficient OLs, were consistent with mTORC1-related deficits. However, deletion of the mTOR signaling-repressor Pten in Ral-deficient OL-lineage cells is unable to rescue mTORC1 activation or developmental myelination deficiencies. Induced deletion of Ral GTPases in OLs of adult mice results in late-onset myelination defects and tissue degeneration. Together, our data indicate critical roles for Ral GTPases to promote developmental spinal cord myelination, to ensure accurate mTORC1 signaling, and to protect the healthy state of myelin-axon units over time. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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