title: DAPK interacts with Patronin and the microtubule cytoskeleton in epidermal development and wound repair.
abstract: Epidermal barrier epithelia form a first line of defense against the environment, protecting animals against infection and repairing physical damage. InC. elegans,death-associated protein kinase (DAPK-1) regulates epidermal morphogenesis, innate immunity and wound repair. Combining genetic suppressor screens and pharmacological tests, we find that DAPK-1 maintains epidermal tissue integrity through regulation of the microtubule (MT) cytoskeleton.dapk-1epidermal phenotypes are suppressed by treatment with microtubule-destabilizing drugs and mimicked or enhanced by microtubule-stabilizing drugs. Loss of function inptrn-1, theC. elegansmember of the Patronin/Nezha/CAMSAP family of MT minus-end binding proteins, suppressesdapk-1epidermal and innate immunity phenotypes. Over-expression of the MT-binding CKK domain of PTRN-1 triggers epidermal and immunity defects resembling those ofdapk-1mutants, and PTRN-1 localization is regulated by DAPK-1. DAPK-1 and PTRN-1 physically interact in co-immunoprecipitation experiments, and DAPK-1 itself undergoes MT-dependent transport. Our results uncover an unexpected interdependence of DAPK-1 and the microtubule cytoskeleton in maintenance of epidermal integrity.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.
authors.forename: Marian
authors.initials: M
authors.lastname: Chuang
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.
authors.forename: Tiffany I
authors.initials: TI
authors.lastname: Hsiao
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Tong
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.
authors.forename: Suhong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, San Diego, United States.
authors.forename: Andrew D
authors.identifier: 0000-0001-5091-0537
authors.initials: AD
authors.lastname: Chisholm
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D004817:Epidermis / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014945:Wound Healing
chemical_list: D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins; C000599463:PTRN-1 protein, C elegans; D064550:Death-Associated Protein Kinases
keywords: C. elegans; CAMSAP; Patronin; cell biology; developmental biology; epithelial cells; stem cells; suppression