title: Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.
abstract: A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties.
authors.affiliation: Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Samar
authors.initials: S
authors.lastname: Sayedyahossein
authors.affiliation: Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Alena
authors.initials: A
authors.lastname: Rudkouskaya
authors.affiliation: Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Leclerc
authors.affiliation: Department of Physiology and Pharmacology, Children's Health Research Institute and Lawson Health Research Institute, The University of Western Ontario, London, Ontario, Canada. Electronic address: ldagnino@uwo.ca.
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D044169:Receptors, Calcium-Sensing; D000099200:Scaffold Protein ILK