title: A Role for DLK in Microtubule Reorganization to the Cell Periphery and in the Maintenance of Desmosomal and Tight Junction Integrity.
abstract: Dual leucine zipper-bearing kinase (DLK) is an inducer of keratinocyte differentiation, a complex process also involving microtubule reorganization to the cell periphery. However, signaling mechanisms involved in this process remain to be elucidated. Here, we demonstrate that DLK enhances and is required for microtubule reorganization to the cell periphery in human cell culture models and in Dlk knockout mouse embryos. In tissue-engineered skins with reduced DLK expression, cortical distribution of two microtubule regulators, LIS1 and HSP27, is impaired as well as desmosomal and tight junction integrity. Altered cortical distribution of desmosomal and tight junction proteins was also confirmed in Dlk knockout mouse embryos. Finally, desmosomal and tight junction defects were also observed after microtubule disruption in nocodazole-treated tissue-engineered skins, thus confirming a role for microtubules in the maintenance of these types of cell junctions. Globally, this study demonstrates that DLK is a key regulator of microtubule reorganization to the cell periphery during keratinocyte differentiation and that this process is required for the maintenance of desmosomal and tight junction integrity.
authors: Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec, Québec, Canada; Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
authors: Carolyne
authors: C
authors: Simard-Bisson
authors: Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec, Québec, Canada.
authors: Julie
authors: J
authors: Bidoggia
authors: Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec, Québec, Canada; Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
authors: Danielle
authors: D
authors: Larouche
authors: Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec, Québec, Canada; Centre Universitaire d'Ophtalmologie (CUO)-Recherche, Québec, Québec, Canada; Département d'Ophtalmologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
authors: Sylvain L
authors: SL
authors: Guérin
authors: Département de biologie, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors: Richard
authors: R
authors: Blouin
authors: Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Biology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors: Syu-Ichi
authors: SI
authors: Hirai
authors: Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec, Québec, Canada; Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, Québec, Canada; Département d'Ophtalmologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada. Electronic address: lucie.germain@fmed.ulaval.ca.
authors: Lucie
authors: L
authors: Germain
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003896:Desmosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology*; D010766:Phosphorylation; D034622:RNA Interference; D012380:Role; D018709:Statistics, Nonparametric; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015739:Nocodazole