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The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle

The normal function of heart muscle depends on its ability to contract more strongly at longer length. Increased venous filling stretches relaxed heart muscle cells, triggering a stronger contraction in the next beat- the Frank-Starling relation. Conversely, heart muscle cells are inactivated when t...

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Autores principales: Kampourakis, Thomas, Irving, Malcolm
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421338/
https://www.ncbi.nlm.nih.gov/pubmed/34489440
http://dx.doi.org/10.1038/s41467-021-25601-8
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author Kampourakis, Thomas
Irving, Malcolm
author_facet Kampourakis, Thomas
Irving, Malcolm
author_sort Kampourakis, Thomas
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description The normal function of heart muscle depends on its ability to contract more strongly at longer length. Increased venous filling stretches relaxed heart muscle cells, triggering a stronger contraction in the next beat- the Frank-Starling relation. Conversely, heart muscle cells are inactivated when they shorten during ejection, accelerating relaxation to facilitate refilling before the next beat. Although both effects are essential for the efficient function of the heart, the underlying mechanisms were unknown. Using bifunctional fluorescent probes on the regulatory light chain of the myosin motor we show that its N-terminal domain may be captured in the folded OFF state of the myosin dimer at the end of the working-stroke of the actin-attached motor, whilst its C-terminal domain joins the OFF state only after motor detachment from actin. We propose that sequential folding of myosin motors onto the filament backbone may be responsible for shortening-induced de-activation in the heart.
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spelling pubmed-84213382021-09-22 The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle Kampourakis, Thomas Irving, Malcolm Nat Commun Article The normal function of heart muscle depends on its ability to contract more strongly at longer length. Increased venous filling stretches relaxed heart muscle cells, triggering a stronger contraction in the next beat- the Frank-Starling relation. Conversely, heart muscle cells are inactivated when they shorten during ejection, accelerating relaxation to facilitate refilling before the next beat. Although both effects are essential for the efficient function of the heart, the underlying mechanisms were unknown. Using bifunctional fluorescent probes on the regulatory light chain of the myosin motor we show that its N-terminal domain may be captured in the folded OFF state of the myosin dimer at the end of the working-stroke of the actin-attached motor, whilst its C-terminal domain joins the OFF state only after motor detachment from actin. We propose that sequential folding of myosin motors onto the filament backbone may be responsible for shortening-induced de-activation in the heart. Nature Publishing Group UK 2021-09-06 /pmc/articles/PMC8421338/ /pubmed/34489440 http://dx.doi.org/10.1038/s41467-021-25601-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kampourakis, Thomas
Irving, Malcolm
The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
title The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
title_full The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
title_fullStr The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
title_full_unstemmed The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
title_short The regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
title_sort regulatory light chain mediates inactivation of myosin motors during active shortening of cardiac muscle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421338/
https://www.ncbi.nlm.nih.gov/pubmed/34489440
http://dx.doi.org/10.1038/s41467-021-25601-8
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