Loss of Protein-tyrosine Phosphatase α (PTPα) Increases Proliferation and Delays Maturation of Oligodendrocyte Progenitor Cells

Wang, Pei-Shan; Wang, Jing; Zheng, Yi; Pallen, Catherine J.

doi:10.1074/jbc.m111.312769

Cited by 11 publications

(8 citation statements)

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“…Ranjan and Hudson found that PTP inhibitors decreased OL differentiation, and Ptpre , together with other PTP, was expressed in differentiating CG4 cells ( 18 ). Other PTPs have a role in OL maturation and myelination; Ptpa loss increased OPC proliferation ( 52 ); Ptprz knock out mice did not recover from EAE as well as controls and remyelination in MS plaques was associated with an upregulation of PTPRZ ( 53 ); also, hypomyelination was observed in Ptpre knock out mice ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Increases Myelination in Oligodendrocytes: Gene Expression Profiling Reveals Early Induction of Genes Involved in Lipid Transport and Metabolism

et al. 2017

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Several studies have shown that erythropoietin (EPO) has neuroprotective or neuroreparative actions on diseases of the nervous system and that improves oligodendrocyte (OL) differentiation and myelination in vivo and in vitro. This study aims at investigating the early molecular mechanisms for the pro-myelinating action of EPO at the gene expression level. For this purpose, we used a differentiating OL precursor cell line, rat central glia-4 cells. Cells were differentiated or not, and then treated with EPO for 1 or 20 h. RNA was extracted and changes in the gene expression profile were assessed using microarray analysis. Experiments were performed in biological replicates of n = 4. Differentiation alone changed the expression of 11% of transcripts (2,663 out of 24,272), representing 2,436 genes, half of which were upregulated and half downregulated. At 20 h of treatment, EPO significantly affected the expression of 99 genes that were already regulated by differentiation and of 150 genes that were not influenced by differentiation alone. Analysis of the transcripts most upregulated by EPO identified several genes involved in lipid transport (e.g., Cd36) and lipid metabolism (Ppargc1a/Pgc1alpha, Lpin1, Pnlip, Lpin2, Ppard, Plin2) along with Igf1 and Igf2, growth factors known for their pro-myelinating action. All these genes were only induced by EPO and not by differentiation alone, except for Pnlip which was highly induced by differentiation and augmented by EPO. Results were validated by quantitative PCR. These findings suggest that EPO might increase remyelination by inducing insulin-like growth factors and increasing lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin Increases Myelination in Oligodendrocytes: Gene Expression Profiling Reveals Early Induction of Genes Involved in Lipid Transport and Metabolism

et al. 2017

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“…Cultures of PTPα-/- OPCs have enhanced proliferation and survival and reduced growth factor dependence. PTPα-/- mice have increased oligodendrocyte lineage cells in the embryonic forebrain and delayed OPC development, with fewer mature oligodendrocytes in the early postnatal corpus callosum (Wang et al, 2012). In contrast, PTPβ/ζ negatively regulates proliferation as well as oligodendrocyte differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…PTPβ/ζ-deficient mice have increased proliferation and early differentiation of OPCs in both the brain and optic nerve. At P10, PTPβ/ζ- /- mice have more myelinated axons in the corpus callosum, though normal levels by 3 months of age (Kuboyama et al, 2012; Wang et al, 2012). PTPε, on the other hand, appears to promote oligodendrocyte differentiation and myelination.…”

Section: Introductionmentioning

confidence: 99%

“…For example, major substrates of PTPα are the Src family kinases (Pallen, 2003). In primary OPCs, PTPα acts through the Src kinase Fyn to negatively regulate the activity of Rho, Rac1, and Cdc42, thereby limiting proliferation and promoting differentiation (Pallen, 2003; Wang et al, 2012). In contrast, in differentiating oligodendrocytes, PTPα positively regulates Rac1 and Cdc42, while negatively regulating Rho signaling, which promotes cytoskeletal rearrangements necessary for process extension and maturation (Wang et al, 2012; 2009).…”

Section: Introductionmentioning

confidence: 99%

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Inhibitors of myelination: ECM changes, CSPGs and PTPs

Harlow

Macklin

2014

Experimental Neurology

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After inflammation-induced demyelination, such as in the disease multiple sclerosis, endogenous remyelination often fails. However, in animal models of demyelination induced with toxins, remyelination can be quite robust. A significant difference between inflammation-induced and toxin-induced demyelination is the response of local cells within the lesion, including astrocytes, oligodendrocytes, microglia/macrophages, and NG2+ cells, which respond to inflammatory stimuli with increased extracellular matrix (ECM) protein and chondroitin sulfate proteoglycan (CSPG) production and deposition. Here, we summarize current knowledge of ECM changes in demyelinating lesions, as well as oligodendrocyte responses to aberrant ECM proteins and CSPGs after various types of demyelinating insults. The discovery that CSPGs act through the receptor protein tyrosine phosphatase sigma (PTPσ) and the Rho-ROCK pathway to inhibit oligodendrocyte process extension and myelination, but not oligodendrocyte differentiation (Pendleton et al., Experimental Neurology (2013) vol. 247, pp. 113-121), highlights the need to better understand the ECM changes that accompany demyelination and their influence on oligodendrocytes and effective remyelination.

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“…Previous work from our laboratory has shown that PTPα regulates Cdc42 activation in a variety of signaling and cell contexts, notably including integrin-induced signaling in fibroblasts ( Samayawardhena and Pallen, 2008 ; Wang et al. , 2009 , 2012 ; Sun et al. , 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Receptor-type protein tyrosine phosphatase alpha (PTPα) mediates MMP14 localization and facilitates triple-negative breast cancer cell invasion

Decotret

Wadsworth

et al. 2021

MBoC

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The ability of cancer cells to invade into surrounding tissues requires degradation of the extracellular matrix (ECM). Invasive structures, such as invadopodia, form on the plasma membrane of cancer cells and secrete ECM-degrading proteases that play crucial roles in cancer cell invasion. We have previously shown that protein tyrosine phosphatase alpha (PTPα) regulates focal adhesion formation and migration of normal cells. Here we report a novel role for PTPα in promoting triple-negative breast cancer cell invasion in vitro and in vivo. We show that PTPα knockdown reduces ECM degradation and cellular invasion of MDA-MB-231 cells through Matrigel. PTPα is not a component of TKS5-positive structures resembling invadopodia; rather, PTPα localizes with endosomal structures positive for MMP14, caveolin-1, and early endosome antigen 1. Furthermore, PTPα regulates MMP14 localization to plasma membrane protrusions, suggesting a role for PTPα in intracellular trafficking of MMP14. Importantly, we show that orthotopic MDA-MB-231 tumours depleted of PTPα exhibit reduced invasion into the surrounding mammary fat pad. These findings suggest a novel role for PTPα in regulating the invasion of triple-negative breast cancer cells.

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Loss of Protein-tyrosine Phosphatase α (PTPα) Increases Proliferation and Delays Maturation of Oligodendrocyte Progenitor Cells

Cited by 11 publications

References 64 publications

Erythropoietin Increases Myelination in Oligodendrocytes: Gene Expression Profiling Reveals Early Induction of Genes Involved in Lipid Transport and Metabolism

Erythropoietin Increases Myelination in Oligodendrocytes: Gene Expression Profiling Reveals Early Induction of Genes Involved in Lipid Transport and Metabolism

Inhibitors of myelination: ECM changes, CSPGs and PTPs

Receptor-type protein tyrosine phosphatase alpha (PTPα) mediates MMP14 localization and facilitates triple-negative breast cancer cell invasion

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