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. 1993 Jun 1;121(5):1133–1140. doi: 10.1083/jcb.121.5.1133

Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein

PMCID: PMC2119693  PMID: 8501118

Abstract

The cadherin cell adhesion system plays a central role in cell-cell adhesion in vertebrates, but its homologues are not identified in the invertebrate. alpha-Catenins are a group of proteins associated with cadherins, and this association is crucial for the cadherins' function. Here, we report the cloning of a Drosophila alpha-catenin gene by low stringent hybridization with a mouse alpha E-catenin probe. Isolated cDNAs encoded a 110-kD protein with 60% identity to mouse alpha E- catenin, and this protein was termed D alpha-catenin. The gene of this protein was located at the chromosome band 80B. Immunostaining analysis using a mAb to D alpha-catenin revealed that it was localized to cell- cell contact sites, expressed throughout development and present in a wide variety of tissues. When this protein was immunoprecipitated from detergent extracts of Drosophila embryos or cell lines, several proteins co-precipitated. These included the armadillo product which was known to be a Drosophila homologue of beta-catenin, another cadherin-associated protein in vertebrates, and a 150-kD glycoprotein. These results strongly suggest that Drosophila has a cell adhesion machinery homologous to the vertebrate cadherin-catenin system.

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Selected References

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  1. Bieber A. J., Snow P. M., Hortsch M., Patel N. H., Jacobs J. R., Traquina Z. R., Schilling J., Goodman C. S. Drosophila neuroglian: a member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1. Cell. 1989 Nov 3;59(3):447–460. doi: 10.1016/0092-8674(89)90029-9. [DOI] [PubMed] [Google Scholar]
  2. Bogaert T., Brown N., Wilcox M. The Drosophila PS2 antigen is an invertebrate integrin that, like the fibronectin receptor, becomes localized to muscle attachments. Cell. 1987 Dec 24;51(6):929–940. doi: 10.1016/0092-8674(87)90580-0. [DOI] [PubMed] [Google Scholar]
  3. Brower D. L., Wilcox M., Piovant M., Smith R. J., Reger L. A. Related cell-surface antigens expressed with positional specificity in Drosophila imaginal discs. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7485–7489. doi: 10.1073/pnas.81.23.7485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coutu M. D., Craig S. W. cDNA-derived sequence of chicken embryo vinculin. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8535–8539. doi: 10.1073/pnas.85.22.8535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Geiger B. A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells. Cell. 1979 Sep;18(1):193–205. doi: 10.1016/0092-8674(79)90368-4. [DOI] [PubMed] [Google Scholar]
  6. Geiger B., Tokuyasu K. T., Dutton A. H., Singer S. J. Vinculin, an intracellular protein localized at specialized sites where microfilament bundles terminate at cell membranes. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4127–4131. doi: 10.1073/pnas.77.7.4127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grenningloh G., Bieber A. J., Rehm E. J., Snow P. M., Traquina Z. R., Hortsch M., Patel N. H., Goodman C. S. Molecular genetics of neuronal recognition in Drosophila: evolution and function of immunoglobulin superfamily cell adhesion molecules. Cold Spring Harb Symp Quant Biol. 1990;55:327–340. doi: 10.1101/sqb.1990.055.01.034. [DOI] [PubMed] [Google Scholar]
  8. Helzlsouer K. J., Gordon G. B., Alberg A. J., Bush T. L., Comstock G. W. Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer. Cancer Res. 1992 Jan 1;52(1):1–4. [PubMed] [Google Scholar]
  9. Herrenknecht K., Ozawa M., Eckerskorn C., Lottspeich F., Lenter M., Kemler R. The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9156–9160. doi: 10.1073/pnas.88.20.9156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirano S., Kimoto N., Shimoyama Y., Hirohashi S., Takeichi M. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992 Jul 24;70(2):293–301. doi: 10.1016/0092-8674(92)90103-j. [DOI] [PubMed] [Google Scholar]
  11. Hirano S., Ui K., Miyake T., Uemura T., Takeichi M. Drosophila PS integrins recognize vertebrate vitronectin and function as cell-substratum adhesion receptors in vitro. Development. 1991 Nov;113(3):1007–1016. doi: 10.1242/dev.113.3.1007. [DOI] [PubMed] [Google Scholar]
  12. Hortsch M., Goodman C. S. Cell and substrate adhesion molecules in Drosophila. Annu Rev Cell Biol. 1991;7:505–557. doi: 10.1146/annurev.cb.07.110191.002445. [DOI] [PubMed] [Google Scholar]
  13. Jonas E., Sargent T. D., Dawid I. B. Epidermal keratin gene expressed in embryos of Xenopus laevis. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5413–5417. doi: 10.1073/pnas.82.16.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knudsen K. A., Wheelock M. J. Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin. J Cell Biol. 1992 Aug;118(3):671–679. doi: 10.1083/jcb.118.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  16. Leptin M., Bogaert T., Lehmann R., Wilcox M. The function of PS integrins during Drosophila embryogenesis. Cell. 1989 Feb 10;56(3):401–408. doi: 10.1016/0092-8674(89)90243-2. [DOI] [PubMed] [Google Scholar]
  17. MacKrell A. J., Blumberg B., Haynes S. R., Fessler J. H. The lethal myospheroid gene of Drosophila encodes a membrane protein homologous to vertebrate integrin beta subunits. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2633–2637. doi: 10.1073/pnas.85.8.2633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Magee A. I., Buxton R. S. Transmembrane molecular assemblies regulated by the greater cadherin family. Curr Opin Cell Biol. 1991 Oct;3(5):854–861. doi: 10.1016/0955-0674(91)90060-c. [DOI] [PubMed] [Google Scholar]
  19. Mahoney P. A., Weber U., Onofrechuk P., Biessmann H., Bryant P. J., Goodman C. S. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell. 1991 Nov 29;67(5):853–868. doi: 10.1016/0092-8674(91)90359-7. [DOI] [PubMed] [Google Scholar]
  20. McCrea P. D., Gumbiner B. M. Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure. J Biol Chem. 1991 Mar 5;266(7):4514–4520. [PubMed] [Google Scholar]
  21. McCrea P. D., Turck C. W., Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991 Nov 29;254(5036):1359–1361. doi: 10.1126/science.1962194. [DOI] [PubMed] [Google Scholar]
  22. Montell D. J., Goodman C. S. Drosophila substrate adhesion molecule: sequence of laminin B1 chain reveals domains of homology with mouse. Cell. 1988 May 6;53(3):463–473. doi: 10.1016/0092-8674(88)90166-3. [DOI] [PubMed] [Google Scholar]
  23. Nagafuchi A., Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988 Dec 1;7(12):3679–3684. doi: 10.1002/j.1460-2075.1988.tb03249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nagafuchi A., Takeichi M. Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. Cell Regul. 1989 Nov;1(1):37–44. doi: 10.1091/mbc.1.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nagafuchi A., Takeichi M., Tsukita S. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991 May 31;65(5):849–857. doi: 10.1016/0092-8674(91)90392-c. [DOI] [PubMed] [Google Scholar]
  26. Nelson W. J., Shore E. M., Wang A. Z., Hammerton R. W. Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1990 Feb;110(2):349–357. doi: 10.1083/jcb.110.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nüsslein-Volhard C., Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980 Oct 30;287(5785):795–801. doi: 10.1038/287795a0. [DOI] [PubMed] [Google Scholar]
  28. Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ozawa M., Ringwald M., Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4246–4250. doi: 10.1073/pnas.87.11.4246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Peifer M., McCrea P. D., Green K. J., Wieschaus E., Gumbiner B. M. The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. J Cell Biol. 1992 Aug;118(3):681–691. doi: 10.1083/jcb.118.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Peifer M., Rauskolb C., Williams M., Riggleman B., Wieschaus E. The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation. Development. 1991 Apr;111(4):1029–1043. doi: 10.1242/dev.111.4.1029. [DOI] [PubMed] [Google Scholar]
  32. Peifer M., Wieschaus E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell. 1990 Dec 21;63(6):1167–1176. doi: 10.1016/0092-8674(90)90413-9. [DOI] [PubMed] [Google Scholar]
  33. Perrimon N., Engstrom L., Mahowald A. P. Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. Genetics. 1989 Feb;121(2):333–352. doi: 10.1093/genetics/121.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Perrimon N., Mahowald A. P. Multiple functions of segment polarity genes in Drosophila. Dev Biol. 1987 Feb;119(2):587–600. doi: 10.1016/0012-1606(87)90061-3. [DOI] [PubMed] [Google Scholar]
  35. Riggleman B., Schedl P., Wieschaus E. Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell. 1990 Nov 2;63(3):549–560. doi: 10.1016/0092-8674(90)90451-j. [DOI] [PubMed] [Google Scholar]
  36. Seeger M. A., Haffley L., Kaufman T. C. Characterization of amalgam: a member of the immunoglobulin superfamily from Drosophila. Cell. 1988 Nov 18;55(4):589–600. doi: 10.1016/0092-8674(88)90217-6. [DOI] [PubMed] [Google Scholar]
  37. Snow P. M., Bieber A. J., Goodman C. S. Fasciclin III: a novel homophilic adhesion molecule in Drosophila. Cell. 1989 Oct 20;59(2):313–323. doi: 10.1016/0092-8674(89)90293-6. [DOI] [PubMed] [Google Scholar]
  38. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
  39. Takeichi M. Cadherins: a molecular family important in selective cell-cell adhesion. Annu Rev Biochem. 1990;59:237–252. doi: 10.1146/annurev.bi.59.070190.001321. [DOI] [PubMed] [Google Scholar]
  40. Tomlinson A., Ready D. F. Neuronal differentiation in Drosophila ommatidium. Dev Biol. 1987 Apr;120(2):366–376. doi: 10.1016/0012-1606(87)90239-9. [DOI] [PubMed] [Google Scholar]
  41. Tsukita S., Tsukita S., Nagafuchi A., Yonemura S. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Curr Opin Cell Biol. 1992 Oct;4(5):834–839. doi: 10.1016/0955-0674(92)90108-o. [DOI] [PubMed] [Google Scholar]
  42. Ui K., Ueda R., Miyake T. Cell lines from imaginal discs of Drosophila melanogaster. In Vitro Cell Dev Biol. 1987 Oct;23(10):707–711. doi: 10.1007/BF02620984. [DOI] [PubMed] [Google Scholar]

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