Crossman, DJ, Jayasinghe, ID orcid.org/0000-0003-2461-478X and Soeller, C (2017) Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma? Biophysical Reviews, 9 (6). pp. 919-929. ISSN 1867-2450
Abstract
Transverse (t)-tubules are invaginations of the plasma membrane that form a complex network of ducts, 200–400 nm in diameter depending on the animal species, that penetrates deep within the cardiac myocyte, where they facilitate a fast and synchronous contraction across the entire cell volume. There is now a large body of evidence in animal models and humans demonstrating that pathological distortion of the t-tubule structure has a causative role in the loss of myocyte contractility that underpins many forms of heart failure. Investigations into the molecular mechanisms of pathological t-tubule remodelling to date have focused on proteins residing in the intracellular aspect of t-tubule membrane that form linkages between the membrane and myocyte cytoskeleton. In this review, we shed light on the mechanisms of t-tubule remodelling which are not limited to the intracellular side. Our recent data have demonstrated that collagen is an integral part of the t-tubule network and that it increases within the tubules in heart failure, suggesting that a fibrotic mechanism could drive cardiac junctional remodelling. We examine the evidence that the linkages between the extracellular matrix, t-tubule membrane and cellular cytoskeleton should be considered as a whole when investigating the mechanisms of t-tubule pathology in the failing heart.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany. This is an author produced version of a paper published in Biophysical Reviews. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Transverse tubules; Excitation–contraction coupling; Heart failure; Extracellular matrix; Collagen |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number Royal Society RG2016R1 Wellcome Trust 207684/Z/17/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Aug 2017 09:42 |
Last Modified: | 10 Jul 2018 00:38 |
Status: | Published |
Publisher: | Springer Verlag |
Identification Number: | 10.1007/s12551-017-0273-7 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119677 |