A G protein-coupled receptor with low density lipoprotein-binding motifs suggests a role for lipoproteins in G-linked signal transduction (original) (raw)

Abstract

We have isolated and analyzed a cDNA from the central nervous system of the mollusc Lymnaea stagnalis encoding a putative receptor, which might be a natural hybrid between two different classes of receptor proteins. Preceded by a signal peptide, two types of repeated sequences are present in the N-terminal part of the protein. The first repeat displays a high sequence similarity to the extracellular binding domains of the low density lipoprotein receptor, which binds and internalizes cholesterol-containing apolipoproteins. The second repeat and the C-terminal part of the Lymnaea receptor are very similar to regions of a specific class of guanine nucleotide-binding protein-coupled receptors, the mammalian glycoprotein hormone receptors. The mRNA encoding the receptor is predominantly expressed in a small number of neurons within the central nervous system and to a lesser extent in the heart.

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  1. Becker-André M., Hahlbrock K. Absolute mRNA quantification using the polymerase chain reaction (PCR). A novel approach by a PCR aided transcript titration assay (PATTY). Nucleic Acids Res. 1989 Nov 25;17(22):9437–9446. doi: 10.1093/nar/17.22.9437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birnbaumer L. Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits. Cell. 1992 Dec 24;71(7):1069–1072. doi: 10.1016/s0092-8674(05)80056-x. [DOI] [PubMed] [Google Scholar]
  3. Block L. H., Knorr M., Vogt E., Locher R., Vetter W., Groscurth P., Qiao B. Y., Pometta D., James R., Regenass M. Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism. Proc Natl Acad Sci U S A. 1988 Feb;85(3):885–889. doi: 10.1073/pnas.85.3.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bloem L. J., Yu L. A time-saving method for screening cDNA or genomic libraries. Nucleic Acids Res. 1990 May 11;18(9):2830–2830. doi: 10.1093/nar/18.9.2830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
  6. Bu G., Williams S., Strickland D. K., Schwartz A. L. Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7427–7431. doi: 10.1073/pnas.89.16.7427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. Dirks R. W., Raap A. K., Van Minnen J., Vreugdenhil E., Smit A. B., Van der Ploeg M. Detection of mRNA molecules coding for neuropeptide hormones of the pond snail Lymnaea stagnalis by radioactive and non-radioactive in situ hybridization: a model study for mRNA detection. J Histochem Cytochem. 1989 Jan;37(1):7–14. doi: 10.1177/37.1.2642295. [DOI] [PubMed] [Google Scholar]
  9. Esser V., Limbird L. E., Brown M. S., Goldstein J. L., Russell D. W. Mutational analysis of the ligand binding domain of the low density lipoprotein receptor. J Biol Chem. 1988 Sep 15;263(26):13282–13290. [PubMed] [Google Scholar]
  10. Geraerts W. P., Smit A. B., Li K. W., Hordijk P. L. The Light Green Cells of Lymnaea: a neuroendocrine model system for stimulus-induced expression of multiple peptide genes in a single cell type. Experientia. 1992 May 15;48(5):464–473. doi: 10.1007/BF01928165. [DOI] [PubMed] [Google Scholar]
  11. Gibbons I. R., Asai D. J., Ching N. S., Dolecki G. J., Mocz G., Phillipson C. A., Ren H., Tang W. J., Gibbons B. H. A PCR procedure to determine the sequence of large polypeptides by rapid walking through a cDNA library. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8563–8567. doi: 10.1073/pnas.88.19.8563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gilbert W. Genes-in-pieces revisited. Science. 1985 May 17;228(4701):823–824. doi: 10.1126/science.4001923. [DOI] [PubMed] [Google Scholar]
  13. Gilbert W. Why genes in pieces? Nature. 1978 Feb 9;271(5645):501–501. doi: 10.1038/271501a0. [DOI] [PubMed] [Google Scholar]
  14. Gross B., Misrahi M., Sar S., Milgrom E. Composite structure of the human thyrotropin receptor gene. Biochem Biophys Res Commun. 1991 Jun 14;177(2):679–687. doi: 10.1016/0006-291x(91)91842-z. [DOI] [PubMed] [Google Scholar]
  15. Hepler J. R., Gilman A. G. G proteins. Trends Biochem Sci. 1992 Oct;17(10):383–387. doi: 10.1016/0968-0004(92)90005-t. [DOI] [PubMed] [Google Scholar]
  16. Herz J., Clouthier D. E., Hammer R. E. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Cell. 1992 Oct 30;71(3):411–421. doi: 10.1016/0092-8674(92)90511-a. [DOI] [PubMed] [Google Scholar]
  17. Herz J., Hamann U., Rogne S., Myklebost O., Gausepohl H., Stanley K. K. Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO J. 1988 Dec 20;7(13):4119–4127. doi: 10.1002/j.1460-2075.1988.tb03306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ikuyama S., Niller H. H., Shimura H., Akamizu T., Kohn L. D. Characterization of the 5'-flanking region of the rat thyrotropin receptor gene. Mol Endocrinol. 1992 May;6(5):793–804. doi: 10.1210/mend.6.5.1318504. [DOI] [PubMed] [Google Scholar]
  19. Ji I., Ji T. H. Exons 1-10 of the rat LH receptor encode a high affinity hormone binding site and exon 11 encodes G-protein modulation and a potential second hormone binding site. Endocrinology. 1991 May;128(5):2648–2650. doi: 10.1210/endo-128-5-2648. [DOI] [PubMed] [Google Scholar]
  20. Kennelly P. J., Krebs E. G. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991 Aug 25;266(24):15555–15558. [PubMed] [Google Scholar]
  21. Knol J. C., Weidemann W., Planta R. J., Vreugdenhil E., van Heerikhuizen H. Molecular cloning of G protein alpha subunits from the central nervous system of the mollusc Lymnaea stagnalis. FEBS Lett. 1992 Dec 21;314(3):215–219. doi: 10.1016/0014-5793(92)81474-z. [DOI] [PubMed] [Google Scholar]
  22. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  24. Libert F., Lefort A., Gerard C., Parmentier M., Perret J., Ludgate M., Dumont J. E., Vassart G. Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1250–1255. doi: 10.1016/0006-291x(89)92736-8. [DOI] [PubMed] [Google Scholar]
  25. McFarland K. C., Sprengel R., Phillips H. S., Köhler M., Rosemblit N., Nikolics K., Segaloff D. L., Seeburg P. H. Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science. 1989 Aug 4;245(4917):494–499. doi: 10.1126/science.2502842. [DOI] [PubMed] [Google Scholar]
  26. Minegishi T., Nakamura K., Takakura Y., Ibuki Y., Igarashi M., Minegish T [corrected to Minegishi T. ]. Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun. 1991 Mar 29;175(3):1125–1130. doi: 10.1016/0006-291x(91)91682-3. [DOI] [PubMed] [Google Scholar]
  27. Minegishi T., Nakamura K., Takakura Y., Miyamoto K., Hasegawa Y., Ibuki Y., Igarashi M., Minegish T [corrected to Minegishi T. ]. Cloning and sequencing of human LH/hCG receptor cDNA. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1049–1054. doi: 10.1016/0006-291x(90)91552-4. [DOI] [PubMed] [Google Scholar]
  28. Nazih H., Devred D., Martin-Nizard F., Clavey V., Fruchart J. C., Delbart C. Pertussis toxin sensitive G-protein coupling of HDL receptor to phospholipase C in human platelets. Thromb Res. 1992 Sep 1;67(5):559–567. doi: 10.1016/0049-3848(92)90016-4. [DOI] [PubMed] [Google Scholar]
  29. Nykjaer A., Petersen C. M., Møller B., Jensen P. H., Moestrup S. K., Holtet T. L., Etzerodt M., Thøgersen H. C., Munch M., Andreasen P. A. Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes. J Biol Chem. 1992 Jul 25;267(21):14543–14546. [PubMed] [Google Scholar]
  30. Okamoto T., Murayama Y., Hayashi Y., Inagaki M., Ogata E., Nishimoto I. Identification of a Gs activator region of the beta 2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Cell. 1991 Nov 15;67(4):723–730. doi: 10.1016/0092-8674(91)90067-9. [DOI] [PubMed] [Google Scholar]
  31. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pittman R. N., Ivins J. K., Buettner H. M. Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth. J Neurosci. 1989 Dec;9(12):4269–4286. doi: 10.1523/JNEUROSCI.09-12-04269.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Probst W. C., Snyder L. A., Schuster D. I., Brosius J., Sealfon S. C. Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol. 1992 Jan-Feb;11(1):1–20. doi: 10.1089/dna.1992.11.1. [DOI] [PubMed] [Google Scholar]
  34. Qian Z., Gilbert M. E., Colicos M. A., Kandel E. R., Kuhl D. Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature. 1993 Feb 4;361(6411):453–457. doi: 10.1038/361453a0. [DOI] [PubMed] [Google Scholar]
  35. Roth G. J. Developing relationships: arterial platelet adhesion, glycoprotein Ib, and leucine-rich glycoproteins. Blood. 1991 Jan 1;77(1):5–19. [PubMed] [Google Scholar]
  36. Rothberg J. M., Jacobs J. R., Goodman C. S., Artavanis-Tsakonas S. slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev. 1990 Dec;4(12A):2169–2187. doi: 10.1101/gad.4.12a.2169. [DOI] [PubMed] [Google Scholar]
  37. Russell D. W., Brown M. S., Goldstein J. L. Different combinations of cysteine-rich repeats mediate binding of low density lipoprotein receptor to two different proteins. J Biol Chem. 1989 Dec 25;264(36):21682–21688. [PubMed] [Google Scholar]
  38. Sachinidis A., Locher R., Mengden T., Steiner A., Vetter W. Vasoconstriction: a novel activity for low density lipoprotein. Biochem Biophys Res Commun. 1989 Aug 30;163(1):315–320. doi: 10.1016/0006-291x(89)92137-2. [DOI] [PubMed] [Google Scholar]
  39. Sachinidis A., Locher R., Mengden T., Vetter W. Low-density lipoprotein elevates intracellular calcium and pH in vascular smooth muscle cells and fibroblasts without mediation of LDL receptor. Biochem Biophys Res Commun. 1990 Feb 28;167(1):353–359. doi: 10.1016/0006-291x(90)91772-k. [DOI] [PubMed] [Google Scholar]
  40. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Simon M. I., Strathmann M. P., Gautam N. Diversity of G proteins in signal transduction. Science. 1991 May 10;252(5007):802–808. doi: 10.1126/science.1902986. [DOI] [PubMed] [Google Scholar]
  42. Sugamori K. S., Sunahara R. K., Guan H. C., Bulloch A. G., Tensen C. P., Seeman P., Niznik H. B., Van Tol H. H. Serotonin receptor cDNA cloned from Lymnaea stagnalis. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):11–15. doi: 10.1073/pnas.90.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tensen C. P., Coenen T., van Herp F. Detection of mRNA encoding crustacean hyperglycemic hormone (CHH) in the eyestalk of the crayfish Orconectes limosus using non-radioactive in situ hybridization. Neurosci Lett. 1991 Apr 1;124(2):178–182. doi: 10.1016/0304-3940(91)90088-b. [DOI] [PubMed] [Google Scholar]
  45. Tsai-Morris C. H., Buczko E., Wang W., Xie X. Z., Dufau M. L. Structural organization of the rat luteinizing hormone (LH) receptor gene. J Biol Chem. 1991 Jun 15;266(17):11355–11359. [PubMed] [Google Scholar]
  46. Wu Y. Q., Jorgensen E. V., Handwerger S. High density lipoproteins stimulate placental lactogen release and adenosine 3',5'-monophosphate (cAMP) production in human trophoblast cells: evidence for cAMP as a second messenger in human placental lactogen release. Endocrinology. 1988 Oct;123(4):1879–1884. doi: 10.1210/endo-123-4-1879. [DOI] [PubMed] [Google Scholar]
  47. Xie Y. B., Wang H., Segaloff D. L. Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. J Biol Chem. 1990 Dec 15;265(35):21411–21414. [PubMed] [Google Scholar]
  48. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]
  49. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]