Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.

Autor: Rodríguez-Molina JF; Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, USA., Lopez-Anido C; Comparative Biomedical Sciences Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Ma KH; Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Zhang C; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Olson T; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Muth KN; Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Weider M; Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Svaren J; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2017 Feb; Vol. 140 (3), pp. 368-382. Date of Electronic Publication: 2017 Jan 09.
DOI: 10.1111/jnc.13911
Abstrakt: Schwann cells and oligodendrocytes are the myelinating cells of the peripheral and central nervous system, respectively. Despite having different myelin components and different transcription factors driving their terminal differentiation there are shared molecular mechanisms between the two. Sox10 is one common transcription factor required for several steps in development of myelinating glia. However, other factors are divergent as Schwann cells need the transcription factor early growth response 2/Krox20 and oligodendrocytes require Myrf. Likewise, some signaling pathways, like the Erk1/2 kinases, are necessary in both cell types for proper myelination. Nonetheless, the molecular mechanisms that control this shared signaling pathway in myelinating cells remain only partially characterized. The hypothesis of this study is that signaling pathways that are similarly regulated in both Schwann cells and oligodendrocytes play central roles in coordinating the differentiation of myelinating glia. To address this hypothesis, we have used genome-wide binding data to identify a relatively small set of genes that are similarly regulated by Sox10 in myelinating glia. We chose one such gene encoding Dual specificity phosphatase 15 (Dusp15) for further analysis in Schwann cell signaling. RNA interference and gene deletion by genome editing in cultured RT4 and primary Schwann cells showed Dusp15 is necessary for full activation of Erk1/2 phosphorylation. In addition, we show that Dusp15 represses expression of several myelin genes, including myelin basic protein. The data shown here support a mechanism by which early growth response 2 activates myelin genes, but also induces a negative feedback loop through Dusp15 to limit over-expression of myelin genes.
Competing Interests: DISCLOSURE The authors have no conflict of interest to declare.
(© 2016 International Society for Neurochemistry.)
Databáze: MEDLINE
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