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

Related outputs

The cardio‐respiratory effects of passive heating and the human thermoneutral zone
Henderson, M.E.T., Brayson, D. and Halsey, L.G. 2021. The cardio‐respiratory effects of passive heating and the human thermoneutral zone. Physiological Reports. 9 (16) e14973. https://doi.org/10.14814/phy2.14973

Preprint: Analysis of cardiomyocyte nuclei in human cardiomyopathy reveals orientation dependent defects in shape
Brayson, D., Ehler, E., dos Remedios, C.G. and Shanahan, C.M. 2020. Preprint: Analysis of cardiomyocyte nuclei in human cardiomyopathy reveals orientation dependent defects in shape. medRxiv. https://doi.org/10.1101/2020.08.14.20168310

Right Ventricle Has Normal Myofilament Function But Shows Perturbations in the Expression of Extracellular Matrix Genes in Patients With Tetralogy of Fallot Undergoing Pulmonary Valve Replacement
Brayson, D., Holohan, S-J., Bardswell, S.C., Arno, M., Lu, H., Jensen, H.K., Tran, P.K., Barallobre‐Barreiro, J., Mayr, M., dos Remedios, C.G., Tsang, V.T., Frigiola, A. and Kentish, J.C. 2020. Right Ventricle Has Normal Myofilament Function But Shows Perturbations in the Expression of Extracellular Matrix Genes in Patients With Tetralogy of Fallot Undergoing Pulmonary Valve Replacement. Journal of the American Heart Association. 9 (16) e015342. https://doi.org/10.1161/jaha.119.015342

The nuclear envelope: LINCing tissue mechanics to genome regulation in cardiac and skeletal muscle
Piccus, R. and Brayson, D. 2020. The nuclear envelope: LINCing tissue mechanics to genome regulation in cardiac and skeletal muscle. Biology Letters. 16 (7) 20200302. https://doi.org/10.1098/rsbl.2020.0302

Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies
Brayson, D., Frustaci, A., Verardo, R., Chimenti, C., Russo, M.A., Hayward, R., Ahmad, S.M., Vizcay-Barrena, G., Protti, A., Zammit, P.S., dos Remedios, C.G., Ehler, E., Shah, A.M. and Shanahan, C.M. 2019. Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies. JCI Insight. 4 (22) e126315. https://doi.org/10.1172/jci.insight.126315

Dynamic heart rate response to multi-day unsupported ultra-endurance cycle racing: a case report
Daniel Brayson, Alessandra Frigiola and James E. Clark 2019. Dynamic heart rate response to multi-day unsupported ultra-endurance cycle racing: a case report. Experimental Physiology. 104 (2), pp. 174-179. https://doi.org/10.1113/ep087341

Muscle tensions merge to cause a DNA replication crisis.
Brayson, D., Ho, C.Y. and Shanahan, C.M. 2018. Muscle tensions merge to cause a DNA replication crisis. The Journal of Cell biology. 217 (6), pp. 1891-1893. https://doi.org/10.1083/jcb.201804041

Preprint: Accumulation of prelamin A drives inflammation in the heart with implications for treatment of inherited and acquired cardiomyopathies
Daniel Brayson, Andrea Frustaci, Romina Verardo, Cristina Chimenti, Matteo Antonio Russo, Robert Hayward, Sadia Munir Ahmad, Gema Vizcay-Barrena, Andrea Protti, Peter S. Zammit, Cristobal G. dos Remedios, Elisabeth Ehler, Ajay M. Shah and Catherine M. Shanahan 2018. Preprint: Accumulation of prelamin A drives inflammation in the heart with implications for treatment of inherited and acquired cardiomyopathies. biorxiv.org. https://doi.org/10.1101/457044

Current insights into LMNA cardiomyopathies: Existing models and missing LINCs.
Brayson, D. and Shanahan, C.M. 2017. Current insights into LMNA cardiomyopathies: Existing models and missing LINCs. Nucleus. 8 (1), pp. 17-33. https://doi.org/10.1080/19491034.2016.1260798

Rnd3 induces stress fibres in endothelial cells through RhoB.
Gottesbühren, U., Garg, R., Riou, P., McColl, B., Brayson, D. and Ridley, A.J. 2013. Rnd3 induces stress fibres in endothelial cells through RhoB. Biology Open. 2 (2), pp. 210-216. https://doi.org/10.1242/bio.20123574

Permalink - https://westminsterresearch.westminster.ac.uk/item/w0z49/lamin-a-precursor-localizes-to-the-z-disc-of-sarcomeres-in-the-heart-and-is-dynamically-regulated-in-muscle-cell-differentiation


Share this

Usage statistics

55 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.