A MINIMAL REGION ON THE INTEGRIN BETA-4 SUBUNIT THAT IS CRITICAL TO ITS LOCALIZATION IN HEMIDESMOSOMES REGULATES THE DISTRIBUTION OF HD1 PLECTIN IN COS-7 CELLS/

The integrin alpha 6 beta 4 is a major component of hemidesmosomes, in which it mediates firm adhesion to laminin 5, Previous studies have s hown that the incorporation of alpha 6 beta 4 into hemidesmosomes requ ires a 303 amino acid stretch of the cytoplasmic domain of beta 4, com prising part of the first fibronectin type III (FNIII) repeat, the sec ond FNIII repeat and the segment that connects the second to the third FNIII repeat (connecting segment), Now we have further defined sequen ces within beta 4 that are critical for its localization in hemidesmos omes and we demonstrate that these sequences also induce the redistrib ution of HD1/plectin into junctional complexes containing the integrin alpha 6 beta 4 in COS-7 cells, transfected with cDNAs encoding alpha 6A and beta 4, Truncation of the cytoplasmic domain of beta 4 after am ino acids 1,382 or 1,355 in the connecting segment, by which a potenti al tyrosine activation motif (TAM) is removed, does not prevent the lo calization of alpha 6 beta 4 in hemidesmosomes in the rat bladder carc inoma cell line 804G and neither did it eliminate the ability of alpha 6 beta 4 to change the subcellular distribution of HD1/plectin in COS -7 cells, In contrast, beta 4 subunits in which the entire connecting segment had been deleted or which were truncated after amino acid 1,32 8, which removes almost the complete segment, had lost both of these f unctions, Furthermore, when beta 4 subunits with either a deletion of the second FNIII repeat or a small deletion in this repeat were co-exp ressed with alpha 6, the integrins were not localized in hemidesmosome s and did not induce the redistribution of HD1/plectin in COS-7 cells, Finally, the fourth FNIII repeat of beta 4 could not replace the seco nd in either of these activities, These findings establish that a regi on in beta 4, 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 alpha 6 beta 4 in hemidesmosomes and that it regulates the distribution of HD1/plectin.