The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions

Dysferlinopathies are a group of muscular dystrophies caused by recessive mutations in the DYSF gene encoding the dysferlin protein. Dysferlin is a transmembrane protein involved in several muscle functions like T-tubule maintenance and membrane repair. In 2009, a study showed the existence of fourt...

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Autores principales:	Océane Ballouhey, Sébastien Courrier, Virginie Kergourlay, Svetlana Gorokhova, Mathieu Cerino, Martin Krahn, Nicolas Lévy, Marc Bartoli
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	membrane calpain (CAPN) dysferlin dysferlinopathies neuromuscular disease Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b3937897f7ae4ee98dbe79ca78dc88c3
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spelling	oai:doaj.org-article:b3937897f7ae4ee98dbe79ca78dc88c32021-11-30T13:09:47ZThe Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions2296-634X10.3389/fcell.2021.754555https://doaj.org/article/b3937897f7ae4ee98dbe79ca78dc88c32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.754555/fullhttps://doaj.org/toc/2296-634XDysferlinopathies are a group of muscular dystrophies caused by recessive mutations in the DYSF gene encoding the dysferlin protein. Dysferlin is a transmembrane protein involved in several muscle functions like T-tubule maintenance and membrane repair. In 2009, a study showed the existence of fourteen dysferlin transcripts generated from alternative splicing. We were interested in dysferlin transcripts containing the exon 40a, and among them the transcript 11 which contains all the canonical exons and exon 40a. This alternative exon encodes a protein region that is cleaved by calpains during the muscle membrane repair mechanism. Firstly, we tested the impact of mutations in exon 40a on its cleavability by calpains. We showed that the peptide encoded by the exon 40a domain is resistant to mutations and that calpains cleaved dysferlin in the first part of DYSF exon 40a. To further explore the implication of this transcript in cell functions, we performed membrane repair, osmotic shock, and transferrin assay. Our results indicated that dysferlin transcript 11 is a key factor in the membrane repair process. Moreover, dysferlin transcript 11 participates in other cell functions such as membrane protection and vesicle trafficking. These results support the need to restore the dysferlin transcript containing the alternative exon 40a in patients affected with dysferlinopathy.Océane BallouheySébastien CourrierVirginie KergourlaySvetlana GorokhovaSvetlana GorokhovaMathieu CerinoMathieu CerinoMartin KrahnMartin KrahnNicolas LévyNicolas LévyNicolas LévyMarc BartoliFrontiers Media S.A.articlemembranecalpain (CAPN)dysferlindysferlinopathiesneuromuscular diseaseBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	membrane calpain (CAPN) dysferlin dysferlinopathies neuromuscular disease Biology (General) QH301-705.5
spellingShingle	membrane calpain (CAPN) dysferlin dysferlinopathies neuromuscular disease Biology (General) QH301-705.5 Océane Ballouhey Sébastien Courrier Virginie Kergourlay Svetlana Gorokhova Svetlana Gorokhova Mathieu Cerino Mathieu Cerino Martin Krahn Martin Krahn Nicolas Lévy Nicolas Lévy Nicolas Lévy Marc Bartoli The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
description	Dysferlinopathies are a group of muscular dystrophies caused by recessive mutations in the DYSF gene encoding the dysferlin protein. Dysferlin is a transmembrane protein involved in several muscle functions like T-tubule maintenance and membrane repair. In 2009, a study showed the existence of fourteen dysferlin transcripts generated from alternative splicing. We were interested in dysferlin transcripts containing the exon 40a, and among them the transcript 11 which contains all the canonical exons and exon 40a. This alternative exon encodes a protein region that is cleaved by calpains during the muscle membrane repair mechanism. Firstly, we tested the impact of mutations in exon 40a on its cleavability by calpains. We showed that the peptide encoded by the exon 40a domain is resistant to mutations and that calpains cleaved dysferlin in the first part of DYSF exon 40a. To further explore the implication of this transcript in cell functions, we performed membrane repair, osmotic shock, and transferrin assay. Our results indicated that dysferlin transcript 11 is a key factor in the membrane repair process. Moreover, dysferlin transcript 11 participates in other cell functions such as membrane protection and vesicle trafficking. These results support the need to restore the dysferlin transcript containing the alternative exon 40a in patients affected with dysferlinopathy.
format	article
author	Océane Ballouhey Sébastien Courrier Virginie Kergourlay Svetlana Gorokhova Svetlana Gorokhova Mathieu Cerino Mathieu Cerino Martin Krahn Martin Krahn Nicolas Lévy Nicolas Lévy Nicolas Lévy Marc Bartoli
author_facet	Océane Ballouhey Sébastien Courrier Virginie Kergourlay Svetlana Gorokhova Svetlana Gorokhova Mathieu Cerino Mathieu Cerino Martin Krahn Martin Krahn Nicolas Lévy Nicolas Lévy Nicolas Lévy Marc Bartoli
author_sort	Océane Ballouhey
title	The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
title_short	The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
title_full	The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
title_fullStr	The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
title_full_unstemmed	The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
title_sort	dysferlin transcript containing the alternative exon 40a is essential for myocyte functions
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b3937897f7ae4ee98dbe79ca78dc88c3
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The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions

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