Pinder, J.C. and Taylor-Harris, P. and Hayes, N.V.L. and Gascard, P.D. and Maggs, A.M. and Baines, A.J. (2001) Cytoskeletal Proteins in Heart Muscle. Cellular & molecular biology letters, 5 (2). p. 227. ISSN 1425-8153.
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We are investigating the expression and function of cytoskeletal protein homologues of the red blood cell membrane-associated skeleton, which we have found occur in heart, an organ in which all cell membranes require mechanisms that provide them with resilience against the forces of continuous beating. We find specific isotypes of spectrin and protein 4.1 genes are differentially compartmentalised in cardiomyocytes at the plasma membrane, intercalated discs and nuclei as well as within the contractile machinery of the muscle sarcomere. Four mammalian 4.1 proteins (4.1R, 4.1G, 4,1N and 4.1B) are known. 5’- and 3’-RACE on mouse heart cDNA indicates that exons 14, 15 and 17a of 4.1R and exons 14, 15 and 16 of 4.1G are variably spliced, with intraexon editing of exons 17 and 22. 4.1N and 4.1B each show alternative splicing of exon 16 and editing within the 3’-untranslated region. All genes express a spectrin-actin binding domain. Immunofluorescence studies show all isoforms, other than 4.1B, occur coincident with the Z disc, 4.1R alone is concentrated on the plasma membrane and intercalated disks whilst 4.1G shows perinuclear distribution. Subcellular fractionation of membranes derived from heart tissue substantiates the immunofluorescence. Immunoprecipitation indicates an interaction between 4.1G and bIIS2 spectrin in intracellular membranes. We have postulated that the spectrin network provides the basis for an „accumulation machine” , able to select and draw protein binding partners together locally into a functional unit, the location a- and b-spectrin isoforms probably being governed by the differentially spliced C-termini of the b-spectrin genes. We conclude that 4.1 proteins are located in heart at major internal cardiomyocyte scaffold loci, possibly providing counteraction to contractile strain.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Cell & Developmental Biology Group|
|Depositing User:||Anthony Baines|
|Date Deposited:||29 Oct 2008 16:13|
|Last Modified:||08 Jun 2012 14:28|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/8638 (The current URI for this page, for reference purposes)|
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