Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in oligodendrocyte development.

Journal of Neurochemistry
Emory KuoHolly Colognato

Abstract

Oligodendrocyte progenitor cells first proliferate to generate sufficient cell numbers and then differentiate into myelin-producing oligodendrocytes. The signal transduction mediators that underlie these events, however, remain poorly understood. The tyrosine phosphatase Shp1 has been linked to oligodendrocyte differentiation as Shp1-deficient mice show hypomyelination. The Shp1 homolog, Shp2, has recently been shown to regulate astrogliogenesis, but its role in oligodendrocyte development remains unknown. Here, we report that Shp2 protein levels were developmentally regulated in oligodendrocytes, with Shp2 phosphorylation being promoted by oligodendroglial mitogens but suppressed by laminin, an extracellular matrix protein that promotes oligodendroglial differentiation. In contrast, oligodendrocyte progenitors were found to be unresponsive to mitogens following Shp2, but not Shp1, depletion. In agreement with previous studies, Shp1 depletion led to decreased levels of myelin basic protein in differentiating oligodendrocytes, as well as reduced outgrowth of myelin membrane sheets. Shp2 depletion in contrast did not prevent oligodendrocyte differentiation but promoted expanded myelin membrane outgrowth. Taken together these data...Continue Reading

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Citations

Apr 6, 2013·Neuroscience Bulletin·Jared T Ahrendsen, Wendy Macklin
Mar 22, 2012·The Journal of Biological Chemistry·Xiujie LiuCheng He
Dec 12, 2012·Genes & Cancer·Kazuya MachidaPeter Nollau
Apr 6, 2011·Journal of Cellular Biochemistry·Wei WangG Wayne Zhou
Sep 27, 2014·Seminars in Cell & Developmental Biology·Veronique DubreuilSheila Harroch
Jun 7, 2014·Frontiers in Molecular Neuroscience·Thomas Blank, Marco Prinz
Dec 31, 2016·Cellular and Molecular Neurobiology·Boxiang QiYujia Yang
Jul 10, 2018·Stem Cells International·Chen KanSiying Wang
Nov 23, 2019·Molecular Brain·Minkyung Kang, Yong-Seok Lee
Aug 24, 2017·Scientific Reports·Debyani ChakravartyCameron W Brennan
Aug 19, 2020·Cells·Roberta Romano, Cecilia Bucci

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