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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...

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Autores principales: Weinert, Stefanie, Bergmann, Nora, Luo, Xiuju, Erdmann, Bettina, Gotthardt, Michael
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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