Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination.

Autor:	Wilson ER; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.; Department of Clinical Neurosciences, University of Cambridge, Cambridge, England, UK., Nunes GD; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado, USA., Shen S; Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Moore S; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Gawron J; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Maxwell J; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Syed U; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Hurley E; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Lanka M; Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, New York, USA., Qu J; Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Désaubry L; Center of Research in Biomedicine of Strasbourg, Regenerative Nanomedicine (UMR 1260), INSERM, University of Strasbourg, Strasbourg, France., Wrabetz L; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.; Department of Neurology, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA., Poitelon Y; Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, New York, USA., Feltri ML; Department of Biochemistry, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.; Department of Neurology, Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
Jazyk:	angličtina
Zdroj:	Glia [Glia] 2024 Dec; Vol. 72 (12), pp. 2247-2267. Date of Electronic Publication: 2024 Aug 31.
DOI:	10.1002/glia.24610
Abstrakt:	Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in severe defects in radial sorting and myelination. We show in vivo that Phb2-null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell Phb2. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2-associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that Phb2 may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell. (© 2024 Wiley Periodicals LLC.)
Databáze:	MEDLINE
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