Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

The Src Homology and Collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development

[img]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB
[img] Other (Supplementary Material)
4MB

Item Type:Article
Title:The Src Homology and Collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development
Creators Name:Mlih, M. and Host, L. and Martin, S. and Niederhoffer, N. and Monassier, L. and Terrand, J. and Messaddeq, N. and Radke, M. and Gotthardt, M. and Bruban, V. and Kober, F. and Bernard, M. and Canet-Soulas, E. and Abt-Jijon, F. and Boucher, P. and Matz, R.L.
Abstract:ShcA (Src Homology and Collagen A) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca2+/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere.
Keywords:Adaptor Protein, Gene Knockout, Heart Development, Heart Failure, Molecular Biology, ErbB, ShcA, Z-Disks, Costamere, Animals, Mice, Rats
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:290
Number:4
Page Range:2419-2430
Date:23 January 2015
Official Publication:https://doi.org/10.1074/jbc.M114.597377
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library