دورية أكاديمية
The Protein Tyrosine Phosphatase Shp2 Regulates Oligodendrocyte Differentiation and Early Myelination and Contributes to Timely Remyelination.
| العنوان: | The Protein Tyrosine Phosphatase Shp2 Regulates Oligodendrocyte Differentiation and Early Myelination and Contributes to Timely Remyelination. |
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| المؤلفون: | Ahrendsen JT; Department of Cell and Developmental Biology, and.; Neuroscience Graduate Program and Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, Colorado 80045., Harlow DE; Department of Cell and Developmental Biology, and., Finseth LT; Department of Cell and Developmental Biology, and., Bourne JN; Department of Cell and Developmental Biology, and., Hickey SP; Department of Cell and Developmental Biology, and., Gould EA; Department of Cell and Developmental Biology, and., Culp CM; Department of Cell and Developmental Biology, and., Macklin WB; Department of Cell and Developmental Biology, and Wendy.Macklin@ucdenver.edu.; Neuroscience Graduate Program and Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, Colorado 80045. |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2018 Jan 24; Vol. 38 (4), pp. 787-802. Date of Electronic Publication: 2017 Dec 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| مواضيع طبية MeSH: | Myelin Sheath/*metabolism , Neurogenesis/*physiology , Oligodendroglia/*cytology , Oligodendroglia/*enzymology , Protein Tyrosine Phosphatase, Non-Receptor Type 11/*metabolism, Animals ; Cell Differentiation/physiology ; Female ; Male ; Mice ; Mice, Transgenic ; Oligodendroglia/metabolism ; Zebrafish |
| مستخلص: | Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mammalian target of rapamycin and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance. We also show that Shp2 regulates the timely differentiation of oligodendrocytes following lysolecithin-induced demyelination, although apparently normal remyelination occurs at a delayed time point. These data suggest that Shp2 is a relevant therapeutic target in demyelinating diseases such as multiple sclerosis. SIGNIFICANCE STATEMENT In the present study, we show that the protein phosphatase Shp2 is an important mediator of oligodendrocyte differentiation and myelination, both during developmental myelination as well as during myelin regeneration. We provide important insight into the signaling mechanisms regulating myelination and propose that Shp2 acts as a transient brake to the developmental myelination process. Furthermore, we show that Shp2 regulates oligodendrocyte differentiation following demyelination and therefore has important therapeutic implications in diseases such as multiple sclerosis. (Copyright © 2018 the authors 0270-6474/18/380787-16$15.00/0.) |
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| معلومات مُعتمدة: | F31 NS081834 United States NS NINDS NIH HHS; T32 DC012280 United States DC NIDCD NIH HHS |
| فهرسة مساهمة: | Keywords: Shp2; myelination; oligodendrocyte; remyelination |
| المشرفين على المادة: | EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) |
| تواريخ الأحداث: | Date Created: 20171209 Date Completed: 20190307 Latest Revision: 20190508 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5783963 |
| DOI: | 10.1523/JNEUROSCI.2864-16.2017 |
| PMID: | 29217681 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1529-2401 |
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| DOI: | 10.1523/JNEUROSCI.2864-16.2017 |