title: Integrin-linked kinase and ELMO2 modulate recycling endosomes in keratinocytes.
abstract: The formation of tight cell-cell junctions is essential in the epidermis for its barrier properties. In this tissue, keratinocytes follow a differentiation program tightly associated with their movement from the innermost basal to the outer suprabasal layers, and with changes in their cell-cell adhesion profile. Intercellular adhesion in keratinocytes is mediated through cell-cell contacts, including E-cadherin-based adherens junctions. Although the mechanisms that mediate E-cadherin delivery to the plasma membrane have been widely studied in simple epithelia, this process is less well understood in the stratified epidermis. In this study, we have investigated the role of Engulfment and Cell Motility 2 (ELMO2) and integrin-linked kinase (ILK) in the positioning of E-cadherin-containing recycling endosomes during establishment of cell-cell contacts in differentiating keratinocytes. We now show that induction of keratinocyte differentiation by Ca2+is accompanied by localization of ELMO2 and ILK to Rab4- and Rab11a-containing recycling endosomes. The positioning of long-loop Rab11a-positive endosomes at areas adjacent to cell-cell contacts is disrupted in ELMO2- or ILK-deficient keratinocytes, and is associated with impaired localization of E-cadherin to cell borders. Our studies show a previously unrecognized role for ELMO2 and ILK in modulation of endosomal positioning, which may play key roles in epidermal sheet maintenance and permeability barrier function.
authors.affiliation: Dept. of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Ho
authors.affiliation: Dept. of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Iordanka A
authors.initials: IA
authors.lastname: Ivanova
authors.affiliation: Dept. of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Ontario N6A 5C1, Canada. Electronic address: ldagnino@uwo.ca.
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics*; D022005:Adherens Junctions / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics*; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D015870:Gene Expression; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics*; D021381:Protein Transport; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins; D000099200:Scaffold Protein ILK
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002118:Calcium; D003598:Cytoskeletal Proteins; D017346:Protein Serine-Threonine Kinases; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; D000099200:Scaffold Protein ILK; C000611838:Cdh1 protein, mouse; C544335:Elmo2 protein, mouse
keywords: ELMO2; Integrin-linked kinase; Keratinocyte; Rab11; Recycling endosome