Isoforms of protein 4.1 are differentially distributed in heart muscle cells: Relation of 4.1R and 4.1G to components of the Ca2+ homeostasis system

Pinder, Jennifer C. and Taylor-Harris, Pamela M. and Bennett, Pauline M. and Carter, Edward and Hayes, Nandini V. L. and King, Mikayala D.A. and Holt, Mark R. and Maggs, Alison M. and Gascard, Philippe and Baines, Anthony J. (2012) Isoforms of protein 4.1 are differentially distributed in heart muscle cells: Relation of 4.1R and 4.1G to components of the Ca2+ homeostasis system. Experimental Cell Research, 318 (13). pp. 1467-1479. ISSN 0014-4827. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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The 4.1 proteins are cytoskeletal adaptor proteins that are linked to the control of mechanical stability of certain membranes and to the cellular accumulation and cell surface display of diverse transmembrane proteins. One of the four mammalian 4.1 proteins, 4.1R (80 kDa/120 kDa isoforms), has recently been shown to be required for the normal operation of several ion transporters in the heart (Stagg MA et al. Circ Res, 2008; 103: 855–863). The other three (4.1G, 4.1N and 4.1B) are largely uncharacterised in the heart. Here, we use specific antibodies to characterise their expression, distribution and novel activities in the left ventricle. We detected 4.1R, 4.1G and 4.1N by immunofluorescence and immunoblotting, but not 4.1B. Only one splice variant of 4.1N and 4.1G was seen whereas there are several forms of 4.1R. 4.1N, like 4.1R, was present in intercalated discs, but unlike 4.1R, it was not localised at the lateral plasma membrane. Both 4.1R and 4.1N were in internal structures that, at the level of resolution of the light microscope, were close to the Z-disc (possibly T-tubules). 4.1G was also in intracellular structures, some of which were coincident with sarcoplasmic reticulum. 4.1G existed in an immunoprecipitable complex with spectrin and SERCA2. 80 kDa 4.1R was present in subcellular fractions enriched in intercalated discs, in a complex resistant to solubilization under non-denaturing conditions. At the intercalated disc 4.1R does not colocalise with the adherens junction protein, β-catenin, but does overlap with the other plasma membrane signalling proteins, the Na/K-ATPase and the Na/Ca exchanger NCX1. We conclude that isoforms of 4.1 proteins are differentially compartmentalised in the heart, and that they form specific complexes with proteins central to cardiomyocyte Ca2 + metabolism.

Item Type: Article
Uncontrolled keywords: Cardiac myocytes; Sarcoplasmic reticulum; Intercalated disc; Cytoskeleton; Protein 4.1; Spectrin; SERCA2
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 08 Oct 2012 10:02
Last Modified: 19 Jun 2014 14:53
Resource URI: (The current URI for this page, for reference purposes)
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