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Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo

Activity of the myogenic regulatory protein myocyte enhancer factor-2 (MEF2) is modulated by post-translational modification. We investigated the in vivo phosphorylation of Drosophila MEF2, and identified serine 98 (S98) as a phosphorylated residue. Phospho-mimetic (S98E) and phospho-null (S98A) iso...

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Autores principales: Vishal, Kumar, Barajas Alonso, Elizabeth, DeAguero, Ashley A., Waters, Jennifer A., Chechenova, Maria B., Cripps, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251773/
https://www.ncbi.nlm.nih.gov/pubmed/37184381
http://dx.doi.org/10.1080/10985549.2023.2198167
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author Vishal, Kumar
Barajas Alonso, Elizabeth
DeAguero, Ashley A.
Waters, Jennifer A.
Chechenova, Maria B.
Cripps, Richard M.
author_facet Vishal, Kumar
Barajas Alonso, Elizabeth
DeAguero, Ashley A.
Waters, Jennifer A.
Chechenova, Maria B.
Cripps, Richard M.
author_sort Vishal, Kumar
collection PubMed
description Activity of the myogenic regulatory protein myocyte enhancer factor-2 (MEF2) is modulated by post-translational modification. We investigated the in vivo phosphorylation of Drosophila MEF2, and identified serine 98 (S98) as a phosphorylated residue. Phospho-mimetic (S98E) and phospho-null (S98A) isoforms of MEF2 did not differ from wild-type in their activity in vitro, so we used CRISPR/Cas9 to generate an S98A allele of the endogenous gene. In mutant larvae we observed phenotypes characteristic of reduced MEF2 function, including reduced body wall muscle size and reduced expression of myofibrillar protein genes; conversely,S98A homozygotes showed enhanced MEF2 function through muscle differentiation within the adult myoblasts associated with the wing imaginal disc. In adults, S98A homozygotes were viable with normal mobility, yet showed patterning defects in muscles that were enhanced when the S98A allele was combined with a Mef2 null allele. Overall our data indicate that blocking MEF2 S98 phosphorylation in myoblasts enhances its myogenic capability, whereas blocking S98 phosphorylation in differentiating muscles attenuates MEF2 function. Our studies are among the first to assess the functional significance of MEF2 phosphorylation sites in the intact animal, and suggest that the same modification can have profoundly different effects upon MEF2 function depending upon the developmental context.
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spelling pubmed-102517732023-06-10 Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo Vishal, Kumar Barajas Alonso, Elizabeth DeAguero, Ashley A. Waters, Jennifer A. Chechenova, Maria B. Cripps, Richard M. Mol Cell Biol Genetics and Molecular Biology Activity of the myogenic regulatory protein myocyte enhancer factor-2 (MEF2) is modulated by post-translational modification. We investigated the in vivo phosphorylation of Drosophila MEF2, and identified serine 98 (S98) as a phosphorylated residue. Phospho-mimetic (S98E) and phospho-null (S98A) isoforms of MEF2 did not differ from wild-type in their activity in vitro, so we used CRISPR/Cas9 to generate an S98A allele of the endogenous gene. In mutant larvae we observed phenotypes characteristic of reduced MEF2 function, including reduced body wall muscle size and reduced expression of myofibrillar protein genes; conversely,S98A homozygotes showed enhanced MEF2 function through muscle differentiation within the adult myoblasts associated with the wing imaginal disc. In adults, S98A homozygotes were viable with normal mobility, yet showed patterning defects in muscles that were enhanced when the S98A allele was combined with a Mef2 null allele. Overall our data indicate that blocking MEF2 S98 phosphorylation in myoblasts enhances its myogenic capability, whereas blocking S98 phosphorylation in differentiating muscles attenuates MEF2 function. Our studies are among the first to assess the functional significance of MEF2 phosphorylation sites in the intact animal, and suggest that the same modification can have profoundly different effects upon MEF2 function depending upon the developmental context. Taylor & Francis 2023-05-15 /pmc/articles/PMC10251773/ /pubmed/37184381 http://dx.doi.org/10.1080/10985549.2023.2198167 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Genetics and Molecular Biology
Vishal, Kumar
Barajas Alonso, Elizabeth
DeAguero, Ashley A.
Waters, Jennifer A.
Chechenova, Maria B.
Cripps, Richard M.
Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo
title Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo
title_full Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo
title_fullStr Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo
title_full_unstemmed Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo
title_short Phosphorylation of the Myogenic Factor Myocyte Enhancer Factor-2 Impacts Myogenesis In Vivo
title_sort phosphorylation of the myogenic factor myocyte enhancer factor-2 impacts myogenesis in vivo
topic Genetics and Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251773/
https://www.ncbi.nlm.nih.gov/pubmed/37184381
http://dx.doi.org/10.1080/10985549.2023.2198167
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