title: Targeted ablation of plectin isoform 1 uncovers role of cytolinker proteins in leukocyte recruitment.
abstract: Plectin, a typical cytolinker protein, is essential for skin and skeletal muscle integrity. It stabilizes cells mechanically, regulates cytoskeleton dynamics, and serves as a scaffolding platform for signaling molecules. A variety of isoforms expressed in different tissues and cell types account for this versatility. To uncover the role of plectin 1, the major isoform expressed in tissues of mesenchymal origin, against the background of all other variants, we raised plectin isoform 1-specific antibodies and generated isoform-deficient mice. In contrast to plectin-null mice (lacking all plectin isoforms), which die shortly after birth because of severe skin blistering, plectin isoform 1-deficient mice were viable at birth, had a normal lifespan, and did not display the skin blistering phenotype. However, dermal fibroblasts isolated from plectin 1-deficient mice exhibited abnormalities in their actin cytoskeleton and impaired migration potential. Similarly, plectin 1-deficient T cells isolated from nymph nodes showed diminished chemotactic migration in vitro. Most strikingly, in vivo we found that leukocyte infiltration during wound healing was reduced in the mutant mice. These data show a specific role of a cytolinker protein in immune cell motility. Single isoform-deficient mice thus represent a powerful tool to unravel highly specific functions of plectin variants.
authors.affiliation: Department of Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 4, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Abrahamsberg
authors.forename: Peter
authors.initials: P
authors.lastname: Fuchs
authors.forename: Selma
authors.initials: S
authors.lastname: Osmanagic-Myers
authors.forename: Irmgard
authors.initials: I
authors.lastname: Fischer
authors.forename: Friedrich
authors.initials: F
authors.lastname: Propst
authors.forename: Adelheid
authors.initials: A
authors.lastname: Elbe-Bürger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wiche
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D003238:Connective Tissue / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D005347:Fibroblasts; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051190:Plectin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012868:Skin Abnormalities / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; C495333:Plec protein, mouse; D051190:Plectin; D020033:Protein Isoforms