A recombinant tail-less integrin β4 subunit disrupts hemidesmosomes, but does not suppress α6β4-mediated cell adhesion to laminins

L. Spinardi, S. Einheber, T. Cullen, T. A. Milner, F. G. Giancotti

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To examine the function of the α6β4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant β4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that α6β4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant β4 subunit did not suppress α6β4- mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-B1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous α6β4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail-less β4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less β4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head- less mutant β4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the α6β4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that α6β4-mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin.

Original languageEnglish
Pages (from-to)473-487
Number of pages15
JournalJournal of Cell Biology
Issue number2
Publication statusPublished - 1995


ASJC Scopus subject areas

  • Cell Biology

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