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M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere
Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. Titin's M-line region contains a unique kinase domain that has been proposed to regulate sarcomere assembly via its substrate titin cap (T-cap). In thi...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063865/ https://www.ncbi.nlm.nih.gov/pubmed/16702235 http://dx.doi.org/10.1083/jcb.200601014 |
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author | Weinert, Stefanie Bergmann, Nora Luo, Xiuju Erdmann, Bettina Gotthardt, Michael |
author_facet | Weinert, Stefanie Bergmann, Nora Luo, Xiuju Erdmann, Bettina Gotthardt, Michael |
author_sort | Weinert, Stefanie |
collection | PubMed |
description | Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. Titin's M-line region contains a unique kinase domain that has been proposed to regulate sarcomere assembly via its substrate titin cap (T-cap). In this study, we use a titin M line–deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase. Rather, titin's M-line region is required to form a continuous titin filament and to provide mechanical stability of the embryonic sarcomere. Even without titin integrating into the M band, sarcomeres show proper spacing and alignment of Z discs and M bands but fail to grow laterally and ultimately disassemble. The comparison of disassembly in the developing and mature knockout sarcomere suggests diverse functions for titin's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titin-binding proteins. |
format | Text |
id | pubmed-2063865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20638652007-11-29 M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere Weinert, Stefanie Bergmann, Nora Luo, Xiuju Erdmann, Bettina Gotthardt, Michael J Cell Biol Research Articles Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. Titin's M-line region contains a unique kinase domain that has been proposed to regulate sarcomere assembly via its substrate titin cap (T-cap). In this study, we use a titin M line–deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase. Rather, titin's M-line region is required to form a continuous titin filament and to provide mechanical stability of the embryonic sarcomere. Even without titin integrating into the M band, sarcomeres show proper spacing and alignment of Z discs and M bands but fail to grow laterally and ultimately disassemble. The comparison of disassembly in the developing and mature knockout sarcomere suggests diverse functions for titin's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titin-binding proteins. The Rockefeller University Press 2006-05-22 /pmc/articles/PMC2063865/ /pubmed/16702235 http://dx.doi.org/10.1083/jcb.200601014 Text en Copyright © 2006, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Weinert, Stefanie Bergmann, Nora Luo, Xiuju Erdmann, Bettina Gotthardt, Michael M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
title | M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
title_full | M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
title_fullStr | M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
title_full_unstemmed | M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
title_short | M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
title_sort | m line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063865/ https://www.ncbi.nlm.nih.gov/pubmed/16702235 http://dx.doi.org/10.1083/jcb.200601014 |
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