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Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling

Excitation‐contraction coupling (ECC) is the physiological process in which an electrical signal originating from the central nervous system is converted into muscle contraction. In skeletal muscle tissue, the key step in the molecular mechanism of ECC initiated by the muscle action potential is the...

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Autores principales: Shishmarev, Dmitry, Rowland, Emily, Aditya, Shouvik, Sundararaj, Srinivasan, Oakley, Aaron J., Dulhunty, Angela F., Casarotto, Marco G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019556/
https://www.ncbi.nlm.nih.gov/pubmed/35481653
http://dx.doi.org/10.1002/pro.4311
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author Shishmarev, Dmitry
Rowland, Emily
Aditya, Shouvik
Sundararaj, Srinivasan
Oakley, Aaron J.
Dulhunty, Angela F.
Casarotto, Marco G.
author_facet Shishmarev, Dmitry
Rowland, Emily
Aditya, Shouvik
Sundararaj, Srinivasan
Oakley, Aaron J.
Dulhunty, Angela F.
Casarotto, Marco G.
author_sort Shishmarev, Dmitry
collection PubMed
description Excitation‐contraction coupling (ECC) is the physiological process in which an electrical signal originating from the central nervous system is converted into muscle contraction. In skeletal muscle tissue, the key step in the molecular mechanism of ECC initiated by the muscle action potential is the cooperation between two Ca(2+) channels, dihydropyridine receptor (DHPR; voltage‐dependent L‐type calcium channel) and ryanodine receptor 1 (RyR1). These two channels were originally postulated to communicate with each other via direct mechanical interactions; however, the molecular details of this cooperation have remained ambiguous. Recently, it has been proposed that one or more supporting proteins are in fact required for communication of DHPR with RyR1 during the ECC process. One such protein that is increasingly believed to play a role in this interaction is the SH3 and cysteine‐rich domain‐containing protein 3 (STAC3), which has been proposed to bind a cytosolic portion of the DHPR α(1S) subunit known as the II–III loop. In this work, we present direct evidence for an interaction between a small peptide sequence of the II–III loop and several residues within the SH3 domains of STAC3 as well as the neuronal isoform STAC2. Differences in this interaction between STAC3 and STAC2 suggest that STAC3 possesses distinct biophysical features that are potentially important for its physiological interactions with the II–III loop. Therefore, this work demonstrates an isoform‐specific interaction between STAC3 and the II–III loop of DHPR and provides novel insights into a putative molecular mechanism behind this association in the skeletal muscle ECC process.
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spelling pubmed-90195562022-04-25 Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling Shishmarev, Dmitry Rowland, Emily Aditya, Shouvik Sundararaj, Srinivasan Oakley, Aaron J. Dulhunty, Angela F. Casarotto, Marco G. Protein Sci Full‐length Papers Excitation‐contraction coupling (ECC) is the physiological process in which an electrical signal originating from the central nervous system is converted into muscle contraction. In skeletal muscle tissue, the key step in the molecular mechanism of ECC initiated by the muscle action potential is the cooperation between two Ca(2+) channels, dihydropyridine receptor (DHPR; voltage‐dependent L‐type calcium channel) and ryanodine receptor 1 (RyR1). These two channels were originally postulated to communicate with each other via direct mechanical interactions; however, the molecular details of this cooperation have remained ambiguous. Recently, it has been proposed that one or more supporting proteins are in fact required for communication of DHPR with RyR1 during the ECC process. One such protein that is increasingly believed to play a role in this interaction is the SH3 and cysteine‐rich domain‐containing protein 3 (STAC3), which has been proposed to bind a cytosolic portion of the DHPR α(1S) subunit known as the II–III loop. In this work, we present direct evidence for an interaction between a small peptide sequence of the II–III loop and several residues within the SH3 domains of STAC3 as well as the neuronal isoform STAC2. Differences in this interaction between STAC3 and STAC2 suggest that STAC3 possesses distinct biophysical features that are potentially important for its physiological interactions with the II–III loop. Therefore, this work demonstrates an isoform‐specific interaction between STAC3 and the II–III loop of DHPR and provides novel insights into a putative molecular mechanism behind this association in the skeletal muscle ECC process. John Wiley & Sons, Inc. 2022-04-20 2022-05 /pmc/articles/PMC9019556/ /pubmed/35481653 http://dx.doi.org/10.1002/pro.4311 Text en © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full‐length Papers
Shishmarev, Dmitry
Rowland, Emily
Aditya, Shouvik
Sundararaj, Srinivasan
Oakley, Aaron J.
Dulhunty, Angela F.
Casarotto, Marco G.
Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
title Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
title_full Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
title_fullStr Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
title_full_unstemmed Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
title_short Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
title_sort molecular interactions of stac proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling
topic Full‐length Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019556/
https://www.ncbi.nlm.nih.gov/pubmed/35481653
http://dx.doi.org/10.1002/pro.4311
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