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Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance

Members of the formin family are important for actin filament nucleation and elongation. We have identified a novel striated muscle–specific splice variant of the formin FHOD3 that introduces a casein kinase 2 (CK2) phosphorylation site. The specific targeting of muscle FHOD3 to the myofibrils in ca...

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Autores principales: Iskratsch, Thomas, Lange, Stephan, Dwyer, Joseph, Kho, Ay Lin, dos Remedios, Cris, Ehler, Elisabeth
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002041/
https://www.ncbi.nlm.nih.gov/pubmed/21149568
http://dx.doi.org/10.1083/jcb.201005060
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author Iskratsch, Thomas
Lange, Stephan
Dwyer, Joseph
Kho, Ay Lin
dos Remedios, Cris
Ehler, Elisabeth
author_facet Iskratsch, Thomas
Lange, Stephan
Dwyer, Joseph
Kho, Ay Lin
dos Remedios, Cris
Ehler, Elisabeth
author_sort Iskratsch, Thomas
collection PubMed
description Members of the formin family are important for actin filament nucleation and elongation. We have identified a novel striated muscle–specific splice variant of the formin FHOD3 that introduces a casein kinase 2 (CK2) phosphorylation site. The specific targeting of muscle FHOD3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of CK2. Phosphorylation of muscle FHOD3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes. Furthermore, we show that muscle FHOD3 efficiently promotes the polymerization of actin filaments in cardiomyocytes and that the down-regulation of its expression severely affects myofibril integrity. In murine and human cardiomyopathy, we observe reduced FHOD3 expression with a concomitant isoform switch and change of subcellular targeting. Collectively, our data suggest that a muscle-specific isoform of FHOD3 is required for the maintenance of the contractile structures in heart muscle and that its function is regulated by posttranslational modification.
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spelling pubmed-30020412011-06-13 Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance Iskratsch, Thomas Lange, Stephan Dwyer, Joseph Kho, Ay Lin dos Remedios, Cris Ehler, Elisabeth J Cell Biol Research Articles Members of the formin family are important for actin filament nucleation and elongation. We have identified a novel striated muscle–specific splice variant of the formin FHOD3 that introduces a casein kinase 2 (CK2) phosphorylation site. The specific targeting of muscle FHOD3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of CK2. Phosphorylation of muscle FHOD3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes. Furthermore, we show that muscle FHOD3 efficiently promotes the polymerization of actin filaments in cardiomyocytes and that the down-regulation of its expression severely affects myofibril integrity. In murine and human cardiomyopathy, we observe reduced FHOD3 expression with a concomitant isoform switch and change of subcellular targeting. Collectively, our data suggest that a muscle-specific isoform of FHOD3 is required for the maintenance of the contractile structures in heart muscle and that its function is regulated by posttranslational modification. The Rockefeller University Press 2010-12-13 /pmc/articles/PMC3002041/ /pubmed/21149568 http://dx.doi.org/10.1083/jcb.201005060 Text en © 2010 Iskratsch 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 Research Articles
Iskratsch, Thomas
Lange, Stephan
Dwyer, Joseph
Kho, Ay Lin
dos Remedios, Cris
Ehler, Elisabeth
Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
title Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
title_full Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
title_fullStr Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
title_full_unstemmed Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
title_short Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance
title_sort formin follows function: a muscle-specific isoform of fhod3 is regulated by ck2 phosphorylation and promotes myofibril maintenance
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002041/
https://www.ncbi.nlm.nih.gov/pubmed/21149568
http://dx.doi.org/10.1083/jcb.201005060
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