Cardiac muscle cell cytoskeletal protein 4.1: analysis of transcripts and subcellular location-relevance to membrane integrity, microstructure, and possible role in heart failure.

Taylor-Harris, Pamela M. and Keating, Lisa A. and Maggs, Alison M. and Phillips, Gareth W. and Birks, Emma J. and Franklin, Rodney C.G. and Yacoub, Magdi H. and Baines, Anthony J. and Pinder, Jennifer C. (2005) Cardiac muscle cell cytoskeletal protein 4.1: analysis of transcripts and subcellular location-relevance to membrane integrity, microstructure, and possible role in heart failure. Mammalian Genome , 16 (3). pp. 137-51. ISSN 0938-8990. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1007/s00335-004-2436-7

Abstract

The spectrin-based cytoskeleton assembly has emerged as a major player in heart functioning; however, cardiac protein 4.1, a key constituent, is uncharacterized. Protein 4.1 evolved to protect cell membranes against mechanical stresses and to organize membrane microstructure. 4.1 Proteins are multifunctional and, among other activities, link integral/signaling proteins on the plasma and internal membranes with the spectrin-based cytoskeleton. Four genes, EPB41, EPB41L1, EPB41L2, and EPB41L3 encode proteins 4.1R, 4.1N, 4.1G, and 4.1B, respectively. All are extensively spliced. Different isoforms are expressed according to tissue and developmental state, individual function being controlled through inclusion/exclusion of interactive domains. We have defined mouse and human cardiac 4.1 transcripts; other than 4. 1B in humans, all genes show activity. Cardiac transcripts constitutively include conserved FERM and C-terminal domains; both interact with membrane-bound signaling/transport/cell adhesion molecules. Variable splicing within and adjacent to the central spectrin/actin-binding domain enables regulation of cytoskeleton-binding activity. A novel heart-specific exon occurs in human 4.1G, but not in mouse. Immunofluorescence reveals 4.1 staining within mouse cardiomyocytes; thus, both at the plasma membrane and, interdigitated with sarcomeric myosin, across myofibrils in regions close to the sarcoplasmic reticulum. These are all regions to which spectrin locates. 4.1R in human heart shows similar distribution; however, there is limited plasma membrane staining. We conclude that cardiac 4.1s are highly regulated in their ability to crosslink plasma/integral cell membranes with the spectrin-actin cytoskeleton. We speculate that over the repetitive cycles of heart muscle contraction and relaxation, 4.1s are likely to locate, support, and coordinate functioning of key membrane-bound macromolecular assemblies.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences > Biomedical Research Group
Depositing User: Anthony Baines
Date Deposited: 11 Sep 2009 11:18
Last Modified: 15 Apr 2014 15:54
Resource URI: http://kar.kent.ac.uk/id/eprint/8619 (The current URI for this page, for reference purposes)
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