Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods
Open Access
- 15 April 2021
- journal article
- research article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 32 (8), 769-787
- https://doi.org/10.1091/mbc.e20-05-0332
Abstract
In the central nervous system, oligodendrocyte precursor cells differentiate into oligodendrocytes to wrap their plasma membranes around neuronal axons, generating mature neural networks with myelin sheaths according to spatial and temporal patterns. While myelination is known to be one of the most dynamic cell morphological changes, the overall intrinsic and extrinsic molecular cues controlling myelination remain to be fully clarified. Here, we describe the biphasic roles of Rnd2, an atypical branch of the Rho family GTPase, in oligodendrocyte myelination during development and after maturation in mice. Compared with littermate controls, oligodendrocyte-specific Rnd2 knockout mice exhibit decreased myelin thickness at the onset of myelination but increased myelin thickness in the later period. Larger proportions of Rho kinase and its substrate Mbs, the signaling unit that negatively regulates oligodendrocyte myelination, are phosphorylated at the onset of myelination, while their smaller proportions are phosphorylated in the later period. In addition, we confirm the biphasic role of Rnd2 through experiments with oligodendrocyte-specific Rnd2 transgenic mice. We conclude that Rnd2 positively regulates myelination in the early myelinating period and negatively regulates myelination in the later period. This unique modulator thus plays different roles depending on the myelination period.Keywords
This publication has 37 references indexed in Scilit:
- Oligodendrocyte Development and PlasticityCold Spring Harbor Perspectives in Biology, 2015
- Signaling Networks that Regulate Cell MigrationCold Spring Harbor Perspectives in Biology, 2015
- Elevated Phosphatidylinositol 3,4,5-Trisphosphate in Glia Triggers Cell-Autonomous Membrane Wrapping and MyelinationJournal of Neuroscience, 2010
- Oligodendrocytes: biology and pathologyActa Neuropathologica, 2009
- Functional Genomic Analysis of Oligodendrocyte DifferentiationJournal of Neuroscience, 2006
- Function and regulation of Rnd proteinsNature Reviews Molecular Cell Biology, 2006
- NGF Controls Axonal Receptivity to Myelination by Schwann Cells or OligodendrocytesNeuron, 2004
- Aberrant Growth and Differentiation of Oligodendrocyte Progenitors in Neurofibromatosis Type 1 MutantsJournal of Neuroscience, 2003
- Rapostlin Is a Novel Effector of Rnd2 GTPase Inducing Neurite BranchingOnline Journal of Public Health Informatics, 2002
- Identification of a Novel Human Rho Protein with Unusual Properties: GTPase Deficiency and In Vivo FarnesylationMolecular and Cellular Biology, 1996