Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783479166523408384 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6910826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gonzalezmoralesnicanor myofibrildiameterissetbyafinelytunedmechanismofproteinoligomerizationindrosophila AT xiaoyushu myofibrildiameterissetbyafinelytunedmechanismofproteinoligomerizationindrosophila AT schillingmatthewaaron myofibrildiameterissetbyafinelytunedmechanismofproteinoligomerizationindrosophila AT marescaloceane myofibrildiameterissetbyafinelytunedmechanismofproteinoligomerizationindrosophila AT liaokuoan myofibrildiameterissetbyafinelytunedmechanismofproteinoligomerizationindrosophila AT schockfrieder myofibrildiameterissetbyafinelytunedmechanismofproteinoligomerizationindrosophila |