title: Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity.
abstract: As multicellular organisms evolved a family of cytoskeletal proteins, the keratins (types I and II) expressed in epithelial cells diversified in more than 20 genes in vertebrates. There is no question that keratin filaments confer mechanical stiffness to cells. However, such a number of genes can hardly be explained by evolutionary advantages in mechanical features. The use of transgenic mouse models has revealed unexpected functional relationships between keratin intermediate filaments and intracellular signaling. Accordingly, loss of keratins or mutations in keratins that cause or predispose to human diseases, result in increased sensitivity to apoptosis, regulation of innate immunity, permeabilization of tight junctions, and mistargeting of apical proteins in different epithelia. Precise mechanistic explanations for these phenomena are still lacking. However, immobilization of membrane or cytoplasmic proteins, including chaperones, on intermediate filaments ("scaffolding") appear as common molecular mechanisms and may explain the need for so many different keratin genes in vertebrates.
authors: Department of Cell Biology, Miller School of Medicine, University of Miami , Miami, FL, USA.
authors: Pedro J
authors: PJ
authors: Salas
authors: Department of Cell Biology, Miller School of Medicine, University of Miami , Miami, FL, USA.
authors: Radia
authors: R
authors: Forteza
authors: Department of Cell Biology, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Physiology, Nova Southeastern University, Fort Lauderdale, FL, USA.
authors: Anastasia
authors: A
authors: Mashukova
mesh_terms: D000818:Animals; D017209:Apoptosis; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007633:Keratins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007633:Keratins
keywords: 14-3-3; Akt; Hsp40; Hsp70; NF-kB; apoptosis; atypical PKC; cell signaling; cytokines; inflammation; innate immunity; tight junction