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Vol. 13, Issue 7, 2347-2359, July 2002

Sarcolemmal Organization in Skeletal Muscle Lacking Desmin: Evidence for Cytokeratins Associated with the Membrane Skeleton at Costameres

Andrea O'Neill,^* McRae W. Williams,^* Wendy G. Resneck,^* Derek J. Milner, Yassemi Capetanaki, and Robert J. Bloch^*§

 ^*Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201; and  Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030

The sarcolemma of fast-twitch muscle is organized into "costameres," structures that are oriented transversely, over the Z and M lines of nearby myofibrils, and longitudinally, to form a rectilinear lattice. Here we examine the role of desmin, the major intermediate filament protein of muscle in organizing costameres. In control mouse muscle, desmin is enriched at the sarcolemmal domains that lie over nearby Z lines and that also contain -spectrin. In tibialis anterior muscle from mice lacking desmin due to homologous recombination, most costameres are lost. In myofibers from desmin / quadriceps, by contrast, most costameric structures are stable. Alternatively, Z line domains may be lost, whereas domains oriented longitudinally or lying over M lines are retained. Experiments with pan-specific antibodies to intermediate filament proteins and to cytokeratins suggest that control and desmin / muscles express similar levels of cytokeratins. Cytokeratins concentrate at the sarcolemma at all three domains of costameres when the latter are retained in desmin / muscle and redistribute with -spectrin at the sarcolemma when costameres are lost. Our results suggest that desmin associates with and selectively stabilizes the Z line domains of costameres, but that cytokeratins associate with all three domains of costameres, even in the absence of desmin.

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^§ Corresponding author, at 660 W. Redwood Street, Baltimore, MD 21201. E-mail address: rbloch{at}umaryland.edu.

Present address: Department of Cell and Structural Biology, University of Illinois, Urbana, IL 61801.

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Molecular Biology of the Cell
Vol. 13, 2347-2359, July 2002
Copyright © 2002 by The American Society for Cell Biology

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