title: A novel function for the MAP kinase SMA-5 in intestinal tube stability.
abstract: Intermediate filaments are major cytoskeletal components whose assembly into complex networks and isotype-specific functions are still largely unknown. Caenorhabditis elegans provides an excellent model system to study intermediate filament organization and function in vivo. Its intestinal intermediate filaments localize exclusively to the endotube, a circumferential sheet just below the actin-based terminal web. A genetic screen for defects in the organization of intermediate filaments identified a mutation in the catalytic domain of the MAP kinase 7 orthologue sma-5(kc1) In sma-5(kc1) mutants, pockets of lumen penetrate the cytoplasm of the intestinal cells. These membrane hernias increase over time without affecting epithelial integrity and polarity. A more pronounced phenotype was observed in the deletion allele sma-5(n678) and in intestine-specific sma-5(RNAi) Besides reduced body length, an increased time of development, reduced brood size, and reduced life span were observed in the mutants, indicating compromised food uptake. Ultrastructural analyses revealed that the luminal pockets include the subapical cytoskeleton and coincide with local thinning and gaps in the endotube that are often enlarged in other regions. Increased intermediate filament phosphorylation was detected by two-dimensional immunoblotting, suggesting that loss of SMA-5 function leads to reduced intestinal tube stability due to altered intermediate filament network phosphorylation.
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Geisler
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Gerhardus
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Carberry
authors.affiliation: Department of Biology and Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-0840.
authors.forename: Wayne
authors.initials: W
authors.lastname: Davis
authors.affiliation: Department of Biology and Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-0840.
authors.forename: Erik
authors.initials: E
authors.lastname: Jorgensen
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Richardson
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany rleube@ukaachen.de olaf.bossinger@uk-koeln.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Bossinger
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany rleube@ukaachen.de olaf.bossinger@uk-koeln.de.
authors.forename: Rudolf E
authors.initials: RE
authors.lastname: Leube
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D003599:Cytoskeleton; D007382:Intermediate Filaments / Q000378:metabolism / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000648:ultrastructure; D008870:Microtubules / Q000502:physiology; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; C503591:SMA-5 protein, C elegans