Specificity of PS integrin function during embryogenesis resides in the alpha subunit extracellular domain (original) (raw)

Abstract

We tested the ability of different integrin alpha subunits to substitute for each other during embryonic development. Two alpha subunits, which form heterodimers with the same betaPS subunit, are expressed in complementary tissues in the Drosophila embryo, with alphaPS1 expressed in the epidermis and endoderm, and alphaPS2 expressed in the mesoderm. As a result the two integrin heterodimers are present on opposite surfaces at sites of interaction between the mesoderm and the other cell layers where they are required for normal development. Using the GAL4 system, we are able to rescue fully the embryonic lethality of an alphaPS2 null mutation with a UAS-alphaPS2 transgene, but only partially with a UAS-alphaPS1 gene, due to partial rescue of both muscle and midgut phenotypes. Similarly we are able to rescue the embryonic/first instar larval lethality of an alphaPS1 null mutation gene with UAS-alphaPS1, but only partially with UAS-alphaPS2. Each UAS-alpha gene, when it contains the cytoplasmic domain from the other alpha subunit, maintains an equivalent ability to rescue its own mutation and cannot fully rescue a mutation in the other alpha. We conclude that the two alpha subunits are not equivalent and have distinct functions which reside in the extracellular domains.

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Selected References

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  1. 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]
  2. Brabant M. C., Fristrom D., Bunch T. A., Brower D. L. Distinct spatial and temporal functions for PS integrins during Drosophila wing morphogenesis. Development. 1996 Oct;122(10):3307–3317. doi: 10.1242/dev.122.10.3307. [DOI] [PubMed] [Google Scholar]
  3. Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
  4. Brower D. L., Bunch T. A., Mukai L., Adamson T. E., Wehrli M., Lam S., Friedlander E., Roote C. E., Zusman S. Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila: genetic analysis of the alpha PS1 integrin subunit. Development. 1995 May;121(5):1311–1320. doi: 10.1242/dev.121.5.1311. [DOI] [PubMed] [Google Scholar]
  5. Brower D. L., Piovant M., Reger L. A. Developmental analysis of Drosophila position-specific antigens. Dev Biol. 1985 Mar;108(1):120–130. doi: 10.1016/0012-1606(85)90014-4. [DOI] [PubMed] [Google Scholar]
  6. Brown N. H. Integrins hold Drosophila together. Bioessays. 1993 Jun;15(6):383–390. doi: 10.1002/bies.950150604. [DOI] [PubMed] [Google Scholar]
  7. Brown N. H., King D. L., Wilcox M., Kafatos F. C. Developmentally regulated alternative splicing of Drosophila integrin PS2 alpha transcripts. Cell. 1989 Oct 6;59(1):185–195. doi: 10.1016/0092-8674(89)90880-5. [DOI] [PubMed] [Google Scholar]
  8. Brown N. H. Null mutations in the alpha PS2 and beta PS integrin subunit genes have distinct phenotypes. Development. 1994 May;120(5):1221–1231. doi: 10.1242/dev.120.5.1221. [DOI] [PubMed] [Google Scholar]
  9. Chan B. M., Kassner P. D., Schiro J. A., Byers H. R., Kupper T. S., Hemler M. E. Distinct cellular functions mediated by different VLA integrin alpha subunit cytoplasmic domains. Cell. 1992 Mar 20;68(6):1051–1060. doi: 10.1016/0092-8674(92)90077-p. [DOI] [PubMed] [Google Scholar]
  10. Cheresh D. A., Spiro R. C. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J Biol Chem. 1987 Dec 25;262(36):17703–17711. [PubMed] [Google Scholar]
  11. Doolittle R. F. Stein and Moore Award address. Reconstructing history with amino acid sequences. Protein Sci. 1992 Feb;1(2):191–200. doi: 10.1002/pro.5560010201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gao D., Kimble J. APX-1 can substitute for its homolog LAG-2 to direct cell interactions throughout Caenorhabditis elegans development. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9839–9842. doi: 10.1073/pnas.92.21.9839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Geyer P. K., Corces V. G. Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. Genes Dev. 1987 Nov;1(9):996–1004. doi: 10.1101/gad.1.9.996. [DOI] [PubMed] [Google Scholar]
  14. Gotwals P. J., Fessler L. I., Wehrli M., Hynes R. O. Drosophila PS1 integrin is a laminin receptor and differs in ligand specificity from PS2. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11447–11451. doi: 10.1073/pnas.91.24.11447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gotwals P. J., Paine-Saunders S. E., Stark K. A., Hynes R. O. Drosophila integrins and their ligands. Curr Opin Cell Biol. 1994 Oct;6(5):734–739. doi: 10.1016/0955-0674(94)90101-5. [DOI] [PubMed] [Google Scholar]
  16. Greig S., Akam M. Homeotic genes autonomously specify one aspect of pattern in the Drosophila mesoderm. Nature. 1993 Apr 15;362(6421):630–632. doi: 10.1038/362630a0. [DOI] [PubMed] [Google Scholar]
  17. Haas T. A., Plow E. F. Integrin-ligand interactions: a year in review. Curr Opin Cell Biol. 1994 Oct;6(5):656–662. doi: 10.1016/0955-0674(94)90091-4. [DOI] [PubMed] [Google Scholar]
  18. Hanks M., Wurst W., Anson-Cartwright L., Auerbach A. B., Joyner A. L. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. Science. 1995 Aug 4;269(5224):679–682. doi: 10.1126/science.7624797. [DOI] [PubMed] [Google Scholar]
  19. Hidalgo A., Urban J., Brand A. H. Targeted ablation of glia disrupts axon tract formation in the Drosophila CNS. Development. 1995 Nov;121(11):3703–3712. doi: 10.1242/dev.121.11.3703. [DOI] [PubMed] [Google Scholar]
  20. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  21. Keith T. P., Riley M. A., Kreitman M., Lewontin R. C., Curtis D., Chambers G. Sequence of the structural gene for xanthine dehydrogenase (rosy locus) in Drosophila melanogaster. Genetics. 1987 May;116(1):67–73. doi: 10.1093/genetics/116.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kiehart D. P., Feghali R. Cytoplasmic myosin from Drosophila melanogaster. J Cell Biol. 1986 Oct;103(4):1517–1525. doi: 10.1083/jcb.103.4.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kishimoto T. K., Hollander N., Roberts T. M., Anderson D. C., Springer T. A. Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell. 1987 Jul 17;50(2):193–202. doi: 10.1016/0092-8674(87)90215-7. [DOI] [PubMed] [Google Scholar]
  24. Kusche-Gullberg M., Garrison K., MacKrell A. J., Fessler L. I., Fessler J. H. Laminin A chain: expression during Drosophila development and genomic sequence. EMBO J. 1992 Dec;11(12):4519–4527. doi: 10.1002/j.1460-2075.1992.tb05553.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Roote C. E., Zusman S. Alternatively spliced forms of the Drosophila alphaPS2 subunit of integrin are sufficient for viability and can replace the function of the alphaPS1 subunit of integrin in the retina. Development. 1996 Jun;122(6):1985–1994. doi: 10.1242/dev.122.6.1985. [DOI] [PubMed] [Google Scholar]
  27. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wehrli M., DiAntonio A., Fearnley I. M., Smith R. J., Wilcox M. Cloning and characterization of alpha PS1, a novel Drosophila melanogaster integrin. Mech Dev. 1993 Sep;43(1):21–36. doi: 10.1016/0925-4773(93)90020-x. [DOI] [PubMed] [Google Scholar]
  29. Zavortink M., Bunch T. A., Brower D. L. Functional properties of alternatively spliced forms of the Drosophila PS2 integrin alpha subunit. Cell Adhes Commun. 1993 Dec;1(3):251–264. doi: 10.3109/15419069309097258. [DOI] [PubMed] [Google Scholar]