The β4 subunit cytoplasmic domain mediates the interaction of α6β4 integrin with the cytoskeleton of hemidesmosomes

Laura Spinardi, Yun Ling Ren, Raymond Sanders, Filippo G. Giancotti

Research output: Contribution to journalArticlepeer-review

Abstract

The α6β4 integrin is structurally distinct from all the other known integrins because the cytoplasmic domain of β4 is unusually large and contains four type III fibronectin-like modules toward its C-terminus. To examine the function of the β4 cytoplasmic tail, we have expressed full-length and truncated human β4 cDNAs in rat bladder epithelial 804G cells, which form hemidesmosome-like adhesions in vitro. The cDNA encoded wild-type β4 subunit associated with endogenous α6 and was recruited at the cell surface within hemidesmosome-like adhesions. A recombinant form of β4, lacking almost the entire cytoplasmic domain associated with α6, reached the cell surface but remained diffusely distributed. A β4 molecule lacking almost the entire extracellular portion did not associate with α6 but was correctly targeted to the hemidesmosome-like adhesions. Thus, the cytoplasmic portion of β4 contains sequences that are required and may be sufficient for the assembly of the α6β4 integrin into hemidesmosomes. To localize these sequences we examined the properties of additional mutant forms of β4. A truncated β4 subunit, lacking the most C-terminal pair of type III fibronectin homology domains, was incorporated into hemidesmosome-like adhesions, but another recombinant β4 molecule, lacking both pairs of type III fibronectin repeats, was not. Finally a recombinant β4 molecule, which was created by adjoining the region of the cytoplasmic domain including all type III repeats to the transmembrane segment, was efficiently recruited in hemidesmosome-like adhesions. Taken together these results suggest that the assembly of the α6β4 integrin into hemidesmosomes is mediated by a 303-amino acid region of β4 tail that comprises the first pair of type III fibronectin repeats and the segment between the second and third repeats. These data imply a function of a specific segment of the β4 cytoplasmic domain in interaction with cytoskeletal components of hemidesmosomes.

Original languageEnglish
Pages (from-to)871-884
Number of pages14
JournalMolecular Biology of the Cell
Volume4
Issue number9
Publication statusPublished - Sep 1993

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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