title: Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival.
abstract: The integrin heterodimer alpha 6 beta 4 is expressed in many epithelia and in Schwann cells. In stratified epithelia, alpha 6 beta 4 couple with BPAG1-e and BPAG2 to form hemidesmosomes, attaching externally to laminin and internally to the keratin cytoskeleton. To explore the function of this atypical integrin, and its relation to conventional actin-associated integrins, we targeted the removal of the beta 4 gene in mice. Tissues that express alpha 6 beta 4 are grossly affected. Stratified tissues are devoid of hemidesmosomes, display only a very fragile attachment to the basal lamina, and exhibit signs of degeneration and tissue disorganization. Simple epithelia which express alpha 6 beta 4 are also defective in adherence, even though they do not form hemidesmosomes. In the absence of beta 4, alpha 6 is dramatically downregulated, and other integrins do not appear to compensate for the loss of this heterodimer. These data have important implications for understanding integrin function in cell-substratum adhesion, cell survival and differentiation, and for understanding the role of alpha 6 beta 4 in junctional epidermolysis bullosa, an often lethal human disorder with pathology similar to our mice.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dowling
authors.forename: Q C
authors.initials: QC
authors.lastname: Yu
authors.forename: E
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001768:Blister / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion; D002460:Cell Line; D002470:Cell Survival; D003896:Desmosomes / Q000502:physiology*; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D039663:Integrin beta4; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000648:ultrastructure
chemical_list: D015703:Antigens, CD; D039663:Integrin beta4; D016023:Integrins; D012333:RNA, Messenger