Lamin A precursor localizes to the Z-disc of sarcomeres in the heart and is dynamically regulated in muscle cell differentiation

Brayson, D. and Shanahan, C.M. 2022. Lamin A precursor localizes to the Z-disc of sarcomeres in the heart and is dynamically regulated in muscle cell differentiation. Philosophical Transactions of the Royal Society B: Biological Sciences. 377 (1864) 20210490. https://doi.org/10.1098/rstb.2021.0490

TitleLamin A precursor localizes to the Z-disc of sarcomeres in the heart and is dynamically regulated in muscle cell differentiation
TypeJournal article
AuthorsBrayson, D. and Shanahan, C.M.
Abstract

The lamin A precursor, prelamin A, requires extensive processing to yield mature lamin A and effect its primary function as a structural filament of the nucleoskeleton. When processing is perturbed, nuclear accumulation of prelamin A is toxic and causes laminopathic diseases such as Hutchinson–Gilford progeria syndrome and cardiomyopathy. However, the physiological role of prelamin A is largely unknown and we sought to identify novel insights about this. Using rodent heart tissue, primary cells and the C2C12 model of myofibrillogenesis, we investigated the expression and localization patterns of prelamin A in heart and skeletal muscle cells. We found that endogenous prelamin A was detectable in mouse heart localized to the sarcomere in both adult mouse heart and isolated neonatal rat cardiomyocytes. We investigated the regulation of prelamin A in C2C12 myofibrillogenesis and found it was dynamically regulated and organized into striations upon myofibril formation, colocalizing with the Z-disc protein α-actinin. These data provide evidence that prelamin A is a component of the sarcomere, underpinning a physiological purpose for unprocessed prelamin A.

Article number20210490
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Journal citation377 (1864)
ISSN0962-8436
1471-2970
Year2022
PublisherRoyal Society
Digital Object Identifier (DOI)https://doi.org/10.1098/rstb.2021.0490
PubMed ID36189817
Web address (URL)https://doi.org/10.1098/rstb.2021.0490
Publication dates
Published online03 Oct 2022
Published in print21 Nov 2022

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