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The nuclear envelope in cardiac health and disease

Research output: Chapter in Book/Report/Conference proceedingChapter

Daniel Brayson, Catherine M. Shanahan

Original languageEnglish
Title of host publicationCardiac Cytoarchitecture: How to Maintain a Working Heart
PublisherSpringer International Publishing
Pages161-185
Number of pages25
ISBN (Print)9783319152639, 9783319152622
DOIs
Publication statusPublished - 1 Jan 2015

King's Authors

Abstract

The nuclear envelope (NE) is a double membrane bilayer, which serves to compartmentalise the nuclear environment from the cytoplasm and regulate the movement of molecules in and out of the nucleus. Another important role of the NE is to physically mediate communication between the nuclear and cytoplasmic domains, which is facilitated by the linker of nucleoskeleton to cytoskeleton (LINC) complex consisting of filamentous lamins on the inner surface and large rod-like nesprins on the outer surface, linked by SUN domain proteins that bridge the double membrane bilayer. On the outer membrane, nesprins link, via N-terminal binding domains, to cytoskeletal components such as actin and microtubules. These physical connections allow rapid communication of mechanical perturbations into the nucleus resulting in gene expression responses designed to adapt the cell to environmental changes. Mutations to these components result in disease phenotypes, which vary in severity and tissue specificity and are often broadly termed ‘premature ageing disorders’. One of the key phenotypes frequently present is cardiomyopathy. As a result, the NE is becoming increasingly relevant in the context of cardiac cytoarchitecture. The discovery that cardiomyopathies consistently arise from mutations to lamins in particular and also emerin and nesprins has led to a body of research intended to elucidate the mechanisms leading to NE-associated cardiac decline and accurately define the role of the NE in the cardiomyocyte.

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