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Originally published as MBC in Press, 10.1091/mbc.01-09-0446 on February 28, 2002
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Vol. 13, Issue 5, 1512-1521, May 2002

Utrophin Binds Laterally along Actin Filaments and Can Couple Costameric Actin with Sarcolemma When Overexpressed in Dystrophin-deficient Muscle

Inna N. Rybakova,* Jitandrakumar R. Patel,* Kay E. Davies,dagger Peter D. Yurchenco,Dagger and James M. Ervasti*§

 *Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53706;  dagger Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom; and  Dagger Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Dystrophin is widely thought to mechanically link the cortical cytoskeleton with the muscle sarcolemma. Although the dystrophin homolog utrophin can functionally compensate for dystrophin in mice, recent studies question whether utrophin can bind laterally along actin filaments and anchor filaments to the sarcolemma. Herein, we have expressed full-length recombinant utrophin and show that the purified protein is fully soluble with a native molecular weight and molecular dimensions indicative of monomers. We demonstrate that like dystrophin, utrophin can form an extensive lateral association with actin filaments and protect actin filaments from depolymerization in vitro. However, utrophin binds laterally along actin filaments through contribution of acidic spectrin-like repeats rather than the cluster of basic repeats used by dystrophin. We also show that the defective linkage between costameric actin filaments and the sarcolemma in dystrophin-deficient mdx muscle is rescued by overexpression of utrophin. Our results demonstrate that utrophin and dystrophin are functionally interchangeable actin binding proteins, but that the molecular epitopes important for filament binding differ between the two proteins. More generally, our results raise the possibility that spectrin-like repeats may enable some members of the plakin family of cytolinkers to laterally bind and stabilize actin filaments.

§ Corresponding author. E-mail address: ervasti{at}physiology.wisc.edu.

Molecular Biology of the Cell
Vol. 13, 1512-1521, May 2002
Copyright © 2002 by The American Society for Cell Biology


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