doi: 10.1161/CIRCRESAHA.108.186460
© 2008 American Heart Association, Inc.
Editorials |
Cardiac Cytoskeleton and Arrhythmia
An Unexpected Role for Protein 4.1R in Cardiac Excitability
From the Departments of Internal Medicine (S.R.C., P.J.M.) and Molecular Physiology and Biophysics (P.J.M.), University of Iowa Carver College of Medicine, Iowa City.
Correspondence to Peter J. Mohler, PhD, 285 Newton Rd, CBRB 2283, Iowa City, IA 52242. E-mail peter-mohler@uiowa.edu
See related article, pages 855–863
Key Words: protein 4.1R • arrhythmia • cytoskeleton • spectrin • Na/Ca exchanger
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The cellular activity of both excitable and nonexcitable cells depends on the coordinate activities of membrane ion channels, transporters, pumps, receptors, and cell adhesion molecules. Underlying these integral membrane proteins in metazoan cells is an elaborate cytoskeletal network that defines cell shape and local membrane architecture and provides strength and stability for cell/cell and cell/matrix interactions. Moreover, the metazoan cytoskeleton serves a critical role in the organization, maintenance, and function of specialized membrane domains.1 In the cardiovascular system, the essential role of the submembrane cytoskeleton for membrane protein and cellular function is clearly illustrated by dysfunction in cytoskeletal elements in human disease. In erythrocytes, ankyrin-R and β1-spectrin directly link membrane proteins to the actin cytoskeleton.2 Human loss-of-function mutations in either ANK1 (encodes ankyrin-R) or SPTN1 (encodes β1-spectrin) result in loss of membrane/cytoskeletal coupling, membrane protein instability, and spherocytosis/anemia.3,4 In heart, dysfunction in cytoskeletal proteins including ankyrin-B, ankyrin-G, 
1-syntrophin, and emerin are linked with potentially fatal human arrhythmias caused by loss of proper coupling between plasma or nuclear membrane proteins and the cytoskeletal network.5–7 In this issue of Circulation Research, Stagg et al extend this paradigm by demonstrating an unexpected role for the cytoskeletal protein 4.1R (red cells) in cardiac excitability.8 Specifically, Stagg et al demonstrate that mice lacking protein 4.1R display multiple cardiac phenotypes (bradycardia, prolonged QTc) and aberrant cardiomyocyte electrical activity.8
Two decades ago, a role for protein 4.1 in the regulation of excitable myocyte function would have seemed unlikely. Similar to spectrin and ankyrin,2
Related Article:
Circ. Res. 2008 103: 855-863.