Home LiteratureArticle Details
PMID: 2269668 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes.

The Journal of cell biology ·Vol. 111 ·No. 6 Pt 2 ·1990-12-00 ·Pages 3141-54

Carter WG, Kaur P, Gil SG, Gahr PJ, Wayner EA

Abstract

Basal cells of stratified epidermis are anchored to the basement membrane zone (BMZ) of skin via hemidesmosomes. We previously identified integrin alpha 3 beta 1, in focal adhesions (FAs), of cultured human keratinocytes (HFKs) as a mediator of HFK adhesion to secreted BMZ-like extracellular matrix (ECM; Carter, W.G., E.A. Wayner, T.S. Bouchard, and P. Kaur. 1990. J. Cell Biol. 110: 1387-1404). Here, we have examined the relation of integrins alpha 6 beta 4 and alpha 3 beta 1, to bullous pemphigoid antigen (BPA), a component of hemidesmosomes. We conclude that alpha 6 beta 4 in HFKs localizes in a new stable anchoring contact (SAC) that cooperates with alpha 3 beta 1-FAs to mediate adhesion to ECM, based on the following. (a) Comparison of secreted ECM, with exogenous laminin, fibronectin and collagen identified ECM as the preferred ligand for HFK adhesion and spreading and for formation of both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs. (b) Inhibition of HFK adhesion with combined anti-alpha 3 beta 1 (P1B5) and anti-alpha 6 beta 4 (GoH3) antibodies indicated that both receptors were functional in adhesion to ECM while alpha 3 beta 1 played a dominant role in spreading. (c) alpha 6 beta 4 colocalized with BPA in SACs that were proximal to but excluded from FAs. Both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs were in contact with the adhesion surface as indicated by antibody exclusion and interference reflection microscopy. (d) In contrast to alpha 3 beta 1-FAs, alpha 6 beta 4-SACs were present only in nonmotile cells, not associated with stress fibers, and were relatively stable to detergents and urea, suggesting a nonmotile, or anchoring function for SACs and motility functions for alpha 3 beta 1-FAs. (e) alpha 6 beta 4 formed a detergent-insoluble complex with exogenous ECM in an affinity isolation procedure, confirming the ability of an unidentified ECM ligand to interact with alpha 6 beta 4. (f) We suggest that alpha 6 beta 4/BPA-SACs in culture restrict migration of HFKs on ECM while alpha 3 beta 1-FAs form dynamic adhesions in spreading and migrating cells. alpha 6 beta 4/BPA-SACs in culture bear functional and compositional similarities to hemidesmosomes in skin.

MeSH Terms
Autoantigens/analysis,physiology Carrier Proteins Cell Adhesion/physiology Cells, Cultured Collagen Cytoskeletal Proteins Dystonin Extracellular Matrix/chemistry Humans Integrins/analysis,physiology Intercellular Junctions/chemistry Keratinocytes/chemistry,cytology,ultrastructure Nerve Tissue Proteins Non-Fibrillar Collagens
Chemicals
Autoantigens Carrier Proteins Cytoskeletal Proteins DST protein, human Dystonin Integrins Nerve Tissue Proteins Non-Fibrillar Collagens collagen type XVII Collagen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Carter W G
Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98104.
Kaur P
Gil S G
Gahr P J
Wayner E A
References (51)
51 references, click to expand
  1. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  2. The use of human pemphigoid autoantibodies to study the fate of epidermal basal cell hemidesmosomes after trypsin dissociation.
    J Invest Dermatol. 1985 Oct;85(4):309-13 PMID: 3900228
  3. Structure and function of intercellular junctions.
    Int Rev Cytol. 1974;39:191-283 PMID: 4611943
  4. Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique.
    J Cell Sci. 1976 Jun;21(1):129-59 PMID: 932106
  5. The hemidesmosome: new fine structural features revealed by freeze-fracture techniques.
    Cell Tissue Res. 1976 Sep 20;172(3):289-307 PMID: 825227
  6. Characterization of bullous pemphigoid antigen: a unique basement membrane protein of stratified squamous epithelia.
    Cell. 1981 Jun;24(3):897-903 PMID: 7018697
  7. A monoclonal antibody that blocks the activity of a neurite regeneration-promoting factor: studies on the binding site and its localization in vivo.
    J Cell Biol. 1986 Oct;103(4):1383-98 PMID: 2945826
  8. Type VII collagen is a major structural component of anchoring fibrils.
    J Cell Biol. 1986 Oct;103(4):1577-86 PMID: 3771648
  9. Is the hemidesmosome a half desmosome? An immunological comparison of mammalian desmosomes and hemidesmosomes.
    Cell Motil Cytoskeleton. 1986;6(6):560-9 PMID: 3542242
  10. Integrins: a family of cell surface receptors.
    Cell. 1987 Feb 27;48(4):549-54 PMID: 3028640
  11. Type VII collagen forms an extended network of anchoring fibrils.
    J Cell Biol. 1987 Mar;104(3):611-21 PMID: 3818794
  12. Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique alpha and common beta subunits.
    J Cell Biol. 1987 Oct;105(4):1873-84 PMID: 2822727
  13. Cell surface receptors for extracellular matrix molecules.
    Annu Rev Cell Biol. 1987;3:179-205 PMID: 2825736
  14. Laminin and other basement membrane components.
    Annu Rev Cell Biol. 1987;3:57-85 PMID: 3318883
  15. Cell surface distribution of fibronectin and vitronectin receptors depends on substrate composition and extracellular matrix accumulation.
    J Cell Biol. 1988 Jun;106(6):2171-82 PMID: 2454933
  16. The human laminin receptor is a member of the integrin family of cell adhesion receptors.
    Science. 1988 Sep 2;241(4870):1228-9 PMID: 2970671
  17. Fibronectin and its receptors.
    Annu Rev Biochem. 1988;57:375-413 PMID: 2972252
  18. The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa.
    J Cell Biol. 1988 Nov;107(5):1881-91 PMID: 2846588
  19. Laminin receptor on platelets is the integrin VLA-6.
    Nature. 1988 Dec 1;336(6198):487-9 PMID: 2973567
  20. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton.
    Annu Rev Cell Biol. 1988;4:487-525 PMID: 3058164
  21. Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes.
    J Invest Dermatol. 1989 Feb;92(2):225-30 PMID: 2645368
  22. A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells.
    Cell. 1989 Apr 7;57(1):59-69 PMID: 2467745
  23. Pemphigus and pemphigoid as paradigms of organ-specific, autoantibody-mediated diseases.
    J Clin Invest. 1989 May;83(5):1443-8 PMID: 2651476
  24. A novel integrin (alpha E beta 4) from human epithelial cells suggests a fourth family of integrin adhesion receptors.
    EMBO J. 1989 Mar;8(3):673-80 PMID: 2542022
  25. Mechanism of fibronectin-mediated cell migration: dependence or independence of cell migration susceptibility on RGDS-directed receptor (integrin).
    Exp Cell Res. 1989 Jul;183(1):126-39 PMID: 2544438
  26. Enhancement of vinculin synthesis by migrating stratified squamous epithelium.
    J Cell Biol. 1989 Aug;109(2):571-6 PMID: 2503524
  27. Endocytosis and recycling of the fibronectin receptor in CHO cells.
    EMBO J. 1989 May;8(5):1341-8 PMID: 2527741
  28. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin.
    J Cell Biol. 1989 Sep;109(3):1321-30 PMID: 2527858
  29. Integrin VLA-3: ultrastructural localization at cell-cell contact sites of human cell cultures.
    J Cell Biol. 1989 Oct;109(4 Pt 1):1807-15 PMID: 2677029
  30. Hemidesmosomes, collagen VII, and intermediate filaments in basal cell carcinoma.
    J Invest Dermatol. 1989 Nov;93(5):662-71 PMID: 2477465
  31. Subunit structure of a laminin-binding integrin and localization of its binding site on laminin.
    J Biol Chem. 1989 Nov 15;264(32):19034-8 PMID: 2808408
  32. Structure and function of laminin: anatomy of a multidomain glycoprotein.
    FASEB J. 1990 Feb 1;4(2):148-60 PMID: 2404817
  33. Intra-epidermal retention of type VII collagen in a patient with recessive dystrophic epidermolysis bullosa.
    J Invest Dermatol. 1990 Feb;94(2):261-4 PMID: 2299201
  34. Novel function for beta 1 integrins in keratinocyte cell-cell interactions.
    J Cell Biol. 1990 Mar;110(3):803-15 PMID: 1689734
  35. Expression of extracellular and intracellular bullous pemphigoid antigens at the dermal-epibolic junction in organ culture of human skin.
    J Invest Dermatol. 1990 Mar;94(3):336-40 PMID: 2407787
  36. Amino acid sequence of a novel integrin beta 4 subunit and primary expression of the mRNA in epithelial cells.
    EMBO J. 1990 Mar;9(3):757-63 PMID: 2311577
  37. Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain.
    EMBO J. 1990 Mar;9(3):765-70 PMID: 2311578
  38. Molecular architecture of basement membranes.
    FASEB J. 1990 Apr 1;4(6):1577-90 PMID: 2180767
  39. The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells.
    J Cell Biol. 1990 Apr;110(4):1387-404 PMID: 1691191
  40. Production of rabbit antibodies against carboxy-terminal epitopes encoded by bullous pemphigoid cDNA.
    J Invest Dermatol. 1990 May;94(5):617-23 PMID: 1691240
  41. Human colon carcinoma cells use multiple receptors to adhere to laminin: involvement of alpha 6 beta 4 and alpha 2 beta 1 integrins.
    Cell Regul. 1990 Feb;1(3):249-57 PMID: 2100200
  42. The fine structure of the interrelationship of cells in the human epidermis.
    J Biophys Biochem Cytol. 1958 Sep 25;4(5):529-38 PMID: 13587545
  43. An electron microscope study of the epidermis of mammalian skin in thin sections. I. Dermo-epidermal junction and basal cell layer.
    J Biophys Biochem Cytol. 1955 Sep 25;1(5):429-44 PMID: 13263331
  44. Immunoelectron microscopic studies of the sites of cell-substratum and cell-cell contacts in cultured fibroblasts.
    J Cell Biol. 1982 Oct;95(1):205-22 PMID: 6815205
  45. Hemidesmosome formation in vitro.
    J Cell Biol. 1983 Sep;97(3):849-57 PMID: 6885921
  46. Visualization of cellular focal contacts using a monoclonal antibody to 80 kD serum protein adsorbed on the substratum.
    Exp Cell Res. 1983 Dec;149(2):387-96 PMID: 6357815
  47. Detection of a cytokeratin determinant common to diverse epithelial cells by a broadly cross-reacting monoclonal antibody.
    EMBO J. 1982;1(11):1429-37 PMID: 6202509
  48. The epidermal basement membrane zone--structure, ontogeny, and role in disease.
    J Am Acad Dermatol. 1984 Dec;11(6):1025-37 PMID: 6512049
  49. A pool of bullous pemphigoid antigen(s) is intracellular and associated with the basal cell cytoskeleton-hemidesmosome complex.
    J Invest Dermatol. 1985 Jan;84(1):47-53 PMID: 3880796
  50. Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes.
    J Invest Dermatol. 1985 Mar;84(3):218-24 PMID: 2579167
  51. Hemidesmosome and desmosome morphogenesis during epidermal wound healing.
    J Ultrastruct Res. 1973 Oct;45(1):93-101 PMID: 4750505
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.111.6.3141
Published
1990-12-00
Pages
3141-54
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2116384
Subset
IM
Grants
NCI NIH HHS · R01-CA49259 · United States
External Links
PubMed source DOI: 10.1083/jcb.111.6.3141 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2