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Published 23 July 2001. doi:10.1083/jcb.200103035
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© The Rockefeller University Press, 0021-9525/2001/7/415 $5.00
The Journal of Cell Biology, Volume 154, Number 2, July 23, 2001 415-426

Article

mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes



Mark Bercher1, Jim Wahl1, Bruce E. Vogel2, Charles Lu2, Edward M. Hedgecock2, David H. Hall3 and John D. Plenefisch1

1 Department of Biology, University of Toledo, Toledo, OH 43606
2 Department of Biology, Johns Hopkins University, Baltimore, MD 21218
3 Center for Caenorhabditis elegans Anatomy, Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461

Address correspondence to John Plenefisch, Department of Biology, University of Toledo, Toledo, OH 43606-3390. Tel.: (419) 530-1551. Fax: (419) 530-7737. E-mail: jplenef{at}uoft02.utoledo.edu

Normal locomotion of the nematode Caenorhabditis elegans requires transmission of contractile force through a series of mechanical linkages from the myofibrillar lattice of the body wall muscles, across an intervening extracellular matrix and epithelium (the hypodermis) to the cuticle. Mutations in mua-3 cause a separation of the hypodermis from the cuticle, suggesting this gene is required for maintaining hypodermal–cuticle attachment as the animal grows in size postembryonically. mua-3 encodes a predicted 3,767 amino acid protein with a large extracellular domain, a single transmembrane helix, and a smaller cytoplasmic domain. The extracellular domain contains four distinct protein modules: 5 low density lipoprotein type A, 52 epidermal growth factor, 1 von Willebrand factor A, and 2 sea urchin-enterokinase-agrin modules. MUA-3 localizes to the hypodermal hemidesmosomes and to other sites of mechanically robust transepithelial attachments, including the rectum, vulva, mechanosensory neurons, and excretory duct/pore. In addition, it is shown that MUA-3 colocalizes with cytoplasmic intermediate filaments (IFs) at these sites. Thus, MUA-3 appears to be a protein that links the IF cytoskeleton of nematode epithelia to the cuticle at sites of mechanical stress.

Key Words: Caenorhabditis elegans; cell-adhesion; extracellular matrix receptors; epidermis; intermediate filaments


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