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, NY, USA.; Department of Clinical Neurosciences, Cambridge University, Cambridge, 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, NY, 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, NY, 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, NY, 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, NY, 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, NY, 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, NY, 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, NY, 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, NY, USA., Desaubry L; Center of Research in Biomedicine of Strasbourg, Regenerative Nanomedicine (UMR 1260), INSERM, University of Strasbourg, 67000 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, NY, 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, NY, 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, NY, 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, NY, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 20. Date of Electronic Publication: 2024 Mar 20.
DOI:	10.1101/2024.03.20.585915
Abstrakt:	Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have 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 work, 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 early and severe defects in peripheral nerve development. Using a proteomic approach in vitro , we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on the presence of axonal signals. Furthermore, we show in vivo that loss of Phb2 in mouse Schwann cells causes ineffective proliferation and dysregulation of transcription factors EGR2 (KROX20), POU3F1 (OCT6) and POU3F2 (BRN2) that are necessary for proper Schwann cell maturation. Schwann cell-specific deletion of Jun , a transcription factor associated with negative regulation of myelination, confers partial rescue of the development defect seen in mice lacking Schwann cell Phb2 . This work develops our understanding of Schwann cell biology, revealing that Phb2 may directly or indirectly modulate the timely expression of transcription factors necessary for proper peripheral nervous system development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell. Competing Interests: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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