Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?
Crossman, DJ; Jayasinghe, ID; Soeller, C
Date: 10 July 2017
Journal
Biophysical Reviews
Publisher
Springer Verlag
Publisher DOI
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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 ...
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.
Physics and Astronomy
Faculty of Environment, Science and Economy
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