Tropomyosin 1: multiple roles in the developing heart and in the formation of congenital heart defects

England, Jennifer and Granados-Riveron, Javier T. and Polo-Parada, Luis and Kuriakose, Diji and Moore, Christopher and Brook, J. David and Rutland, Catrin S. and Setchfield, Kerry and Gell, Christopher and Ghosh, Tushar K. and Bu'Lock, Frances A. and Thornborough, Christopher and Ehler, Elisabeth and Loughna, Siobhan (2017) Tropomyosin 1: multiple roles in the developing heart and in the formation of congenital heart defects. Journal of Molecular and Cellular Cardiology, 106 . pp. 1-13. ISSN 1095-8584

[img]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Available under Licence Creative Commons Attribution.
Download (2MB) | Preview

Abstract

Tropomyosin 1 (TPM1) is an essential sarcomeric component, stabilising the thin filament and facilitating actin's interaction with myosin. A number of sarcomeric proteins, such as alpha myosin heavy chain, play crucial roles in cardiac development. Mutations in these genes have been linked to congenital heart defects (CHDs), occurring in approximately 1 in 145 live births. To date, TPM1 has not been associated with isolated CHDs. Analysis of 380 CHD cases revealed three novel mutations in the TPM1 gene; IVS1 + 2T > C, I130V, S229F and a polyadenylation signal site variant GATAAA/AATAAA. Analysis of IVS1 + 2T > C revealed aberrant pre-mRNA splicing. In addition, abnormal structural properties were found in hearts transfected with TPM1 carrying I130V and S229F mutations. Phenotypic analysis of TPM1 morpholino-treated embryos revealed roles for TPM1 in cardiac looping, atrial septation and ventricular trabeculae formation and increased apoptosis was seen within the heart. In addition, sarcomere assembly was affected and altered action potentials were exhibited. This study demonstrated that sarcomeric TPM1 plays vital roles in cardiogenesis and is a suitable candidate gene for screening individuals with isolated CHDs.

Item Type: Article
Keywords: Cardiac development; Congenital heart defects; Structural protein; Tropomyosin 1
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1016/j.yjmcc.2017.03.006
Depositing User: Eprints, Support
Date Deposited: 10 May 2017 14:00
Last Modified: 12 May 2017 09:30
URI: http://eprints.nottingham.ac.uk/id/eprint/42722

Actions (Archive Staff Only)

Edit View Edit View