Abstract
The product of the Toll gene is a membrane protein required for the formation of dorso-ventral polarity during early embryogenesis in Drosophila melanogaster. It acts together with the other dorsal group gene products to specify a nuclear gradient of dorsal morphogen in the syncytial blastoderm stage embryo. Here we report the presence in Toll protein of additional sequences held in common with the human membrane receptor platelet glycoprotein 1b (Gp1b). We propose that these sequences in Toll form disulphide linked extracellular domains that are important for the binding of ligands in the perivitelline space of the embryo. In addition, we show that expression of Toll protein induced in a non-adhesive cell line promotes cellular adhesion, a property held in common with the related Drosophila glycoprotein chaoptin. Toll protein in such aggregates accumulates at sites of cell-cell interaction, a characteristic displayed by other cellular adhesion molecules. Taken together these findings suggest that the biochemical function of Toll protein is more closely analogous to that of Gp1b than previously thought.
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Selected References
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- Anderson K. V., Bokla L., Nüsslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell. 1985 Oct;42(3):791–798. doi: 10.1016/0092-8674(85)90275-2. [DOI] [PubMed] [Google Scholar]
- Anderson K. V., Jürgens G., Nüsslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product. Cell. 1985 Oct;42(3):779–789. doi: 10.1016/0092-8674(85)90274-0. [DOI] [PubMed] [Google Scholar]
- Anderson K. V., Nüsslein-Volhard C. Information for the dorsal--ventral pattern of the Drosophila embryo is stored as maternal mRNA. Nature. 1984 Sep 20;311(5983):223–227. doi: 10.1038/311223a0. [DOI] [PubMed] [Google Scholar]
- Chasan R., Anderson K. V. The role of easter, an apparent serine protease, in organizing the dorsal-ventral pattern of the Drosophila embryo. Cell. 1989 Feb 10;56(3):391–400. doi: 10.1016/0092-8674(89)90242-0. [DOI] [PubMed] [Google Scholar]
- Crouch M. F., Lapetina E. G. A role for Gi in control of thrombin receptor-phospholipase C coupling in human platelets. J Biol Chem. 1988 Mar 5;263(7):3363–3371. [PubMed] [Google Scholar]
- DeLotto R., Spierer P. A gene required for the specification of dorsal-ventral pattern in Drosophila appears to encode a serine protease. Nature. 1986 Oct 23;323(6090):688–692. doi: 10.1038/323688a0. [DOI] [PubMed] [Google Scholar]
- Di Nocera P. P., Dawid I. B. Transient expression of genes introduced into cultured cells of Drosophila. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7095–7098. doi: 10.1073/pnas.80.23.7095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elkins T., Hortsch M., Bieber A. J., Snow P. M., Goodman C. S. Drosophila fasciclin I is a novel homophilic adhesion molecule that along with fasciclin III can mediate cell sorting. J Cell Biol. 1990 May;110(5):1825–1832. doi: 10.1083/jcb.110.5.1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ezzell R. M., Kenney D. M., Egan S., Stossel T. P., Hartwig J. H. Localization of the domain of actin-binding protein that binds to membrane glycoprotein Ib and actin in human platelets. J Biol Chem. 1988 Sep 15;263(26):13303–13309. [PubMed] [Google Scholar]
- Fox J. E., Reynolds C. C., Phillips D. R. Calcium-dependent proteolysis occurs during platelet aggregation. J Biol Chem. 1983 Aug 25;258(16):9973–9981. [PubMed] [Google Scholar]
- Gay N. J., Poole S. J., Kornberg T. B. The Drosophila engrailed protein is phosphorylated by a serine-specific protein kinase. Nucleic Acids Res. 1988 Jul 25;16(14A):6637–6647. doi: 10.1093/nar/16.14.6637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gay N. J., Poole S., Kornberg T. Association of the Drosophila melanogaster engrailed protein with specific soluble nuclear protein complexes. EMBO J. 1988 Dec 20;7(13):4291–4297. doi: 10.1002/j.1460-2075.1988.tb03327.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerttula S., Jin Y. S., Anderson K. V. Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation. Genetics. 1988 May;119(1):123–133. doi: 10.1093/genetics/119.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gélinas C., Temin H. M. The v-rel oncogene encodes a cell-specific transcriptional activator of certain promoters. Oncogene. 1988 Oct;3(4):349–355. [PubMed] [Google Scholar]
- Harmon J. T., Jamieson G. A. The glycocalicin portion of platelet glycoprotein Ib expresses both high and moderate affinity receptor sites for thrombin. A soluble radioreceptor assay for the interaction of thrombin with platelets. J Biol Chem. 1986 Oct 5;261(28):13224–13229. [PubMed] [Google Scholar]
- Hashimoto C., Hudson K. L., Anderson K. V. The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell. 1988 Jan 29;52(2):269–279. doi: 10.1016/0092-8674(88)90516-8. [DOI] [PubMed] [Google Scholar]
- Hoopes B. C., McClure W. R. Studies on the selectivity of DNA precipitation by spermine. Nucleic Acids Res. 1981 Oct 24;9(20):5493–5504. doi: 10.1093/nar/9.20.5493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krantz D. E., Zipursky S. L. Drosophila chaoptin, a member of the leucine-rich repeat family, is a photoreceptor cell-specific adhesion molecule. EMBO J. 1990 Jun;9(6):1969–1977. doi: 10.1002/j.1460-2075.1990.tb08325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Lopez J. A., Chung D. W., Fujikawa K., Hagen F. S., Davie E. W., Roth G. J. The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2135–2139. doi: 10.1073/pnas.85.7.2135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez J. A., Chung D. W., Fujikawa K., Hagen F. S., Papayannopoulou T., Roth G. J. Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5615–5619. doi: 10.1073/pnas.84.16.5615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
- Michelson A. D., Barnard M. R. Thrombin-induced changes in platelet membrane glycoproteins Ib, IX, and IIb-IIIa complex. Blood. 1987 Nov;70(5):1673–1678. [PubMed] [Google Scholar]
- Miller H. Practical aspects of preparing phage and plasmid DNA: growth, maintenance, and storage of bacteria and bacteriophage. Methods Enzymol. 1987;152:145–170. doi: 10.1016/0076-6879(87)52016-x. [DOI] [PubMed] [Google Scholar]
- Nagafuchi A., Shirayoshi Y., Okazaki K., Yasuda K., Takeichi M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature. 1987 Sep 24;329(6137):341–343. doi: 10.1038/329341a0. [DOI] [PubMed] [Google Scholar]
- Nose A., Tsuji K., Takeichi M. Localization of specificity determining sites in cadherin cell adhesion molecules. Cell. 1990 Apr 6;61(1):147–155. doi: 10.1016/0092-8674(90)90222-z. [DOI] [PubMed] [Google Scholar]
- Nüsslein-Volhard C., Frohnhöfer H. G., Lehmann R. Determination of anteroposterior polarity in Drosophila. Science. 1987 Dec 18;238(4834):1675–1681. doi: 10.1126/science.3686007. [DOI] [PubMed] [Google Scholar]
- Okita J. R., Pidard D., Newman P. J., Montgomery R. R., Kunicki T. J. On the association of glycoprotein Ib and actin-binding protein in human platelets. J Cell Biol. 1985 Jan;100(1):317–321. doi: 10.1083/jcb.100.1.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips D. R., Charo I. F., Parise L. V., Fitzgerald L. A. The platelet membrane glycoprotein IIb-IIIa complex. Blood. 1988 Apr;71(4):831–843. [PubMed] [Google Scholar]
- Reinke R., Krantz D. E., Yen D., Zipursky S. L. Chaoptin, a cell surface glycoprotein required for Drosophila photoreceptor cell morphogenesis, contains a repeat motif found in yeast and human. Cell. 1988 Jan 29;52(2):291–301. doi: 10.1016/0092-8674(88)90518-1. [DOI] [PubMed] [Google Scholar]
- Rio D. C., Laski F. A., Rubin G. M. Identification and immunochemical analysis of biologically active Drosophila P element transposase. Cell. 1986 Jan 17;44(1):21–32. doi: 10.1016/0092-8674(86)90481-2. [DOI] [PubMed] [Google Scholar]
- Rio D. C., Rubin G. M. Transformation of cultured Drosophila melanogaster cells with a dominant selectable marker. Mol Cell Biol. 1985 Aug;5(8):1833–1838. doi: 10.1128/mcb.5.8.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg A. H., Lade B. N., Chui D. S., Lin S. W., Dunn J. J., Studier F. W. Vectors for selective expression of cloned DNAs by T7 RNA polymerase. Gene. 1987;56(1):125–135. doi: 10.1016/0378-1119(87)90165-x. [DOI] [PubMed] [Google Scholar]
- Roth S., Stein D., Nüsslein-Volhard C. A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo. Cell. 1989 Dec 22;59(6):1189–1202. doi: 10.1016/0092-8674(89)90774-5. [DOI] [PubMed] [Google Scholar]
- Rushlow C. A., Han K., Manley J. L., Levine M. The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila. Cell. 1989 Dec 22;59(6):1165–1177. doi: 10.1016/0092-8674(89)90772-1. [DOI] [PubMed] [Google Scholar]
- Schneider I. Cell lines derived from late embryonic stages of Drosophila melanogaster. J Embryol Exp Morphol. 1972 Apr;27(2):353–365. [PubMed] [Google Scholar]
- Schüpbach T., Wieschaus E. Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations. Genetics. 1989 Jan;121(1):101–117. doi: 10.1093/genetics/121.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. doi: 10.1093/nar/10.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steward R. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science. 1987 Oct 30;238(4827):692–694. doi: 10.1126/science.3118464. [DOI] [PubMed] [Google Scholar]
- Steward R. Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function. Cell. 1989 Dec 22;59(6):1179–1188. doi: 10.1016/0092-8674(89)90773-3. [DOI] [PubMed] [Google Scholar]
- Steward R., Zusman S. B., Huang L. H., Schedl P. The dorsal protein is distributed in a gradient in early Drosophila embryos. Cell. 1988 Nov 4;55(3):487–495. doi: 10.1016/0092-8674(88)90035-9. [DOI] [PubMed] [Google Scholar]
- Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Takahashi Y., Putnam F. W. Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1906–1910. doi: 10.1073/pnas.82.7.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Titani K., Takio K., Handa M., Ruggeri Z. M. Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5610–5614. doi: 10.1073/pnas.84.16.5610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Vactor D., Jr, Krantz D. E., Reinke R., Zipursky S. L. Analysis of mutants in chaoptin, a photoreceptor cell-specific glycoprotein in Drosophila, reveals its role in cellular morphogenesis. Cell. 1988 Jan 29;52(2):281–290. doi: 10.1016/0092-8674(88)90517-x. [DOI] [PubMed] [Google Scholar]
- Vicente V., Houghten R. A., Ruggeri Z. M. Identification of a site in the alpha chain of platelet glycoprotein Ib that participates in von Willebrand factor binding. J Biol Chem. 1990 Jan 5;265(1):274–280. [PubMed] [Google Scholar]
- Walker J. E., Auffret A. D., Carne A., Gurnett A., Hanisch P., Hill D., Saraste M. Solid-phase sequence analysis of polypeptides eluted from polyacrylamide gels. An aid to interpretation of DNA sequences exemplified by the Escherichia coli unc operon and bacteriophage lambda. Eur J Biochem. 1982 Apr 1;123(2):253–260. doi: 10.1111/j.1432-1033.1982.tb19761.x. [DOI] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]