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Jab1 regulates Schwann cell proliferation and axonal sorting through p27

Axonal sorting is a crucial event in nerve formation and requires proper Schwann cell proliferation, differentiation, and contact with axons. Any defect in axonal sorting results in dysmyelinating peripheral neuropathies. Evidence from mouse models shows that axonal sorting is regulated by laminin21...

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Autores principales: Porrello, Emanuela, Rivellini, Cristina, Dina, Giorgia, Triolo, Daniela, Del Carro, Ubaldo, Ungaro, Daniela, Panattoni, Martina, Feltri, Maria Laura, Wrabetz, Lawrence, Pardi, Ruggero, Quattrini, Angelo, Previtali, Stefano Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892969/
https://www.ncbi.nlm.nih.gov/pubmed/24344238
http://dx.doi.org/10.1084/jem.20130720
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author Porrello, Emanuela
Rivellini, Cristina
Dina, Giorgia
Triolo, Daniela
Del Carro, Ubaldo
Ungaro, Daniela
Panattoni, Martina
Feltri, Maria Laura
Wrabetz, Lawrence
Pardi, Ruggero
Quattrini, Angelo
Previtali, Stefano Carlo
author_facet Porrello, Emanuela
Rivellini, Cristina
Dina, Giorgia
Triolo, Daniela
Del Carro, Ubaldo
Ungaro, Daniela
Panattoni, Martina
Feltri, Maria Laura
Wrabetz, Lawrence
Pardi, Ruggero
Quattrini, Angelo
Previtali, Stefano Carlo
author_sort Porrello, Emanuela
collection PubMed
description Axonal sorting is a crucial event in nerve formation and requires proper Schwann cell proliferation, differentiation, and contact with axons. Any defect in axonal sorting results in dysmyelinating peripheral neuropathies. Evidence from mouse models shows that axonal sorting is regulated by laminin211– and, possibly, neuregulin 1 (Nrg1)–derived signals. However, how these signals are integrated in Schwann cells is largely unknown. We now report that the nuclear Jun activation domain–binding protein 1 (Jab1) may transduce laminin211 signals to regulate Schwann cell number and differentiation during axonal sorting. Mice with inactivation of Jab1 in Schwann cells develop a dysmyelinating neuropathy with axonal sorting defects. Loss of Jab1 increases p27 levels in Schwann cells, which causes defective cell cycle progression and aberrant differentiation. Genetic down-regulation of p27 levels in Jab1-null mice restores Schwann cell number, differentiation, and axonal sorting and rescues the dysmyelinating neuropathy. Thus, Jab1 constitutes a regulatory molecule that integrates laminin211 signals in Schwann cells to govern cell cycle, cell number, and differentiation. Finally, Jab1 may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies.
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spelling pubmed-38929692014-07-13 Jab1 regulates Schwann cell proliferation and axonal sorting through p27 Porrello, Emanuela Rivellini, Cristina Dina, Giorgia Triolo, Daniela Del Carro, Ubaldo Ungaro, Daniela Panattoni, Martina Feltri, Maria Laura Wrabetz, Lawrence Pardi, Ruggero Quattrini, Angelo Previtali, Stefano Carlo J Exp Med Article Axonal sorting is a crucial event in nerve formation and requires proper Schwann cell proliferation, differentiation, and contact with axons. Any defect in axonal sorting results in dysmyelinating peripheral neuropathies. Evidence from mouse models shows that axonal sorting is regulated by laminin211– and, possibly, neuregulin 1 (Nrg1)–derived signals. However, how these signals are integrated in Schwann cells is largely unknown. We now report that the nuclear Jun activation domain–binding protein 1 (Jab1) may transduce laminin211 signals to regulate Schwann cell number and differentiation during axonal sorting. Mice with inactivation of Jab1 in Schwann cells develop a dysmyelinating neuropathy with axonal sorting defects. Loss of Jab1 increases p27 levels in Schwann cells, which causes defective cell cycle progression and aberrant differentiation. Genetic down-regulation of p27 levels in Jab1-null mice restores Schwann cell number, differentiation, and axonal sorting and rescues the dysmyelinating neuropathy. Thus, Jab1 constitutes a regulatory molecule that integrates laminin211 signals in Schwann cells to govern cell cycle, cell number, and differentiation. Finally, Jab1 may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies. The Rockefeller University Press 2014-01-13 /pmc/articles/PMC3892969/ /pubmed/24344238 http://dx.doi.org/10.1084/jem.20130720 Text en © 2014 Porrello et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Porrello, Emanuela
Rivellini, Cristina
Dina, Giorgia
Triolo, Daniela
Del Carro, Ubaldo
Ungaro, Daniela
Panattoni, Martina
Feltri, Maria Laura
Wrabetz, Lawrence
Pardi, Ruggero
Quattrini, Angelo
Previtali, Stefano Carlo
Jab1 regulates Schwann cell proliferation and axonal sorting through p27
title Jab1 regulates Schwann cell proliferation and axonal sorting through p27
title_full Jab1 regulates Schwann cell proliferation and axonal sorting through p27
title_fullStr Jab1 regulates Schwann cell proliferation and axonal sorting through p27
title_full_unstemmed Jab1 regulates Schwann cell proliferation and axonal sorting through p27
title_short Jab1 regulates Schwann cell proliferation and axonal sorting through p27
title_sort jab1 regulates schwann cell proliferation and axonal sorting through p27
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892969/
https://www.ncbi.nlm.nih.gov/pubmed/24344238
http://dx.doi.org/10.1084/jem.20130720
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