mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes.
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.
Bercher
M
M
Department of Biology, University of Toledo, Toledo, OH 43606, USA.
Wahl
J
J
Vogel
B E
BE
Lu
C
C
Hedgecock
E M
EM
Hall
D H
DH
Plenefisch
J D
JD
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics; D004848:Epithelium / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D022002:Hemidesmosomes / Q000378:metabolism; D017270:Lipoprotein(a) / Q000235:genetics; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009928:Organ Specificity; D017434:Protein Structure, Tertiary / Q000502:physiology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D015801:Helminth Proteins; D017270:Lipoprotein(a); C432914:MUA-3 protein, C elegans; D046911:Macromolecular Substances; D008565:Membrane Proteins; D004815:Epidermal Growth Factor