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A minimal region on the integrin β4 subunit that is critical to its localization in hemidesmosomes regulates the distribution of HD1/plectin in COS-7 cells

1997; The Company of Biologists; Volume: 110; Issue: 15 Linguagem: Inglês

10.1242/jcs.110.15.1705

1477-9137

Carien M. Niessen, Esther H. M. Hulsman, Lauran C. J. M. Oomen, Ingrid Kuikman, Arnoud Sonnenberg,

Wnt/β-catenin signaling in development and cancer

ABSTRACT The integrin α6β4 is a major component of hemidesmosomes, in which it mediates firm adhesion to laminin 5. Previous studies have shown that the incorporation of α6β4 into hemidesmosomes requires a 303 amino acid stretch of the cytoplasmic domain of β4, comprising part of the first fibronectin type III (FNIII) repeat, the second FNIII repeat and the segment that connects the second to the third FNIII repeat (connecting segment). Now, we have further defined sequences within β4 that are critical for its localization in hemidesmosomes and we demonstrate that these sequences also induce the redistribution of HD1/plectin into junctional complexes containing the integrin α6β4 in COS-7 cells, transfected with cDNAs encoding α6A and β4. Truncation of the cytoplasmic domain of β4 after amino acids 1,382 or 1,355 in the connecting segment, by which a potential tyrosine activation motif (TAM) is removed, does not prevent the localization of α6β4 in hemidesmosomes in the rat bladder carcinoma cell line 804G and neither did it eliminate the ability of α 6β4 to change the subcellular dis-tribution of HD1/plectin in COS-7 cells. In contrast, β4 subunits in which the entire connecting segment had been deleted or which were truncated after amino acid 1,328, which removes almost the complete segment, had lost both of these functions. Furthermore, when β4 subunits with either a deletion of the second FNIII repeat or a small deletion in this repeat were co-expressed with α6, the integrins were not localized in hemidesmosomes and did not induce the redistribution of HD1/plectin in COS-7 cells. Finally, the fourth FNIII repeat of β4 could not replace the second in either of these activities. These findings establish that a region in β4, which encompasses the second FNIII repeat and a stretch of 27 amino acids (1,329-1,355) of the connecting segment, is critical for the localization of α6β4 in hemidesmosomes and that it regulates the distribution of HD1/plectin.