Effects of beta subunit cytoplasmic domain deletions on the recruitment of the integrin alpha v beta 6 to focal contacts.
The integrin alpha v beta 6 is expressed primarily in epithelial cells and mediates attachment to the extracellular matrix protein fibronectin. We recently observed that alpha v beta 6 localizes to focal contacts when cells that express the receptor are plated on fibronectin. To determine which regions of the beta 6 cytoplasmic domain are required for recruitment to focal contacts, the wild type human beta 6 cytoplasmic domain are required for recruitment to focal contacts, the wild type human beta 6 subunit and mutants containing selective deletions within the beta 6 cytoplasmic domain were stably expressed in Chinese Hamster Ovary cells. The beta 6 cytoplasmic domain is composed of a 41 amino acid region that is highly conserved among integrin beta subunits, and a unique 11 amino acid carboxy terminal extension. The 11 amino acid extension was not required for localization to focal contacts; in fact, its removal appeared to increase receptor localization. However, removal of any of the 3 conserved regions previously identified as important for the localization of beta 1 integrins to focal contacts (Reszka, et al., 1992, J. Cell Biol. 117:1321-30) eliminated recruitment of beta 6 to focal contacts. These data suggest that, as with the integrin beta 1 subunit, multiple regions within the first 41 amino acids of the beta 6 cytoplasmic domain are necessary for recruitment of alpha v beta 6 to focal contacts. However, the unique 11 amino acid carboxy terminus of beta 6 is not required for this recruitment, and may actually play a negative regulatory role.
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Lung Biology Center, University of California, San Francisco 94143-0854.
Weinacker
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Chen
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Sheppard
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D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D001665:Binding Sites; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D002966:Clathrin / Q000378:metabolism; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D014162:Transfection; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D000951:Antigens, Neoplasm; D002966:Clathrin; D016023:Integrins; C073878:integrin alphavbeta6; D016596:Vinculin