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Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila

Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about...

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Autores principales: González-Morales, Nicanor, Xiao, Yu Shu, Schilling, Matthew Aaron, Marescal, Océane, Liao, Kuo An, Schöck, Frieder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910826/
https://www.ncbi.nlm.nih.gov/pubmed/31746737
http://dx.doi.org/10.7554/eLife.50496
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author González-Morales, Nicanor
Xiao, Yu Shu
Schilling, Matthew Aaron
Marescal, Océane
Liao, Kuo An
Schöck, Frieder
author_facet González-Morales, Nicanor
Xiao, Yu Shu
Schilling, Matthew Aaron
Marescal, Océane
Liao, Kuo An
Schöck, Frieder
author_sort González-Morales, Nicanor
collection PubMed
description Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about the underlying mechanisms setting myofibril diameter. Here we show that the PDZ and LIM domain protein Zasp, a structural component of Z-discs, mediates Z-disc and thereby myofibril growth through protein oligomerization. Oligomerization is induced by an interaction of its ZM domain with LIM domains. Oligomerization is terminated upon upregulation of shorter Zasp isoforms which lack LIM domains at later developmental stages. The balance between these two isoforms, which we call growing and blocking isoforms sets the stereotyped diameter of myofibrils. If blocking isoforms dominate, myofibrils become smaller. If growing isoforms dominate, myofibrils and Z-discs enlarge, eventually resulting in large pathological aggregates that disrupt muscle function.
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spelling pubmed-69108262019-12-16 Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila González-Morales, Nicanor Xiao, Yu Shu Schilling, Matthew Aaron Marescal, Océane Liao, Kuo An Schöck, Frieder eLife Cell Biology Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about the underlying mechanisms setting myofibril diameter. Here we show that the PDZ and LIM domain protein Zasp, a structural component of Z-discs, mediates Z-disc and thereby myofibril growth through protein oligomerization. Oligomerization is induced by an interaction of its ZM domain with LIM domains. Oligomerization is terminated upon upregulation of shorter Zasp isoforms which lack LIM domains at later developmental stages. The balance between these two isoforms, which we call growing and blocking isoforms sets the stereotyped diameter of myofibrils. If blocking isoforms dominate, myofibrils become smaller. If growing isoforms dominate, myofibrils and Z-discs enlarge, eventually resulting in large pathological aggregates that disrupt muscle function. eLife Sciences Publications, Ltd 2019-11-20 /pmc/articles/PMC6910826/ /pubmed/31746737 http://dx.doi.org/10.7554/eLife.50496 Text en © 2019, González-Morales et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
González-Morales, Nicanor
Xiao, Yu Shu
Schilling, Matthew Aaron
Marescal, Océane
Liao, Kuo An
Schöck, Frieder
Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
title Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
title_full Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
title_fullStr Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
title_full_unstemmed Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
title_short Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
title_sort myofibril diameter is set by a finely tuned mechanism of protein oligomerization in drosophila
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910826/
https://www.ncbi.nlm.nih.gov/pubmed/31746737
http://dx.doi.org/10.7554/eLife.50496
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