Skip to main content
Genetics logoLink to Genetics
. 2000 May;155(1):85–104. doi: 10.1093/genetics/155.1.85

A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21) regulate a common set of chemosensory behaviors in caenorhabditis elegans.

D A Birnby 1, E M Link 1, J J Vowels 1, H Tian 1, P L Colacurcio 1, J H Thomas 1
PMCID: PMC1461074  PMID: 10790386

Abstract

Caenorhabditis elegans daf-11 and daf-21 mutants share defects in specific chemosensory responses mediated by several classes of sensory neurons, indicating that these two genes have closely related functions in an assortment of chemosensory pathways. We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs). The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process and further suggesting that daf-21 acts at a similar step. daf-11::gfp fusions are expressed in five identified pairs of chemosensory neurons in a pattern consistent with most daf-11 mutant phenotypes. We also show that daf-21 encodes the heat-shock protein 90 (Hsp90), a chaperone with numerous specific protein targets. We show that the viable chemosensory-deficient daf-21 mutation is an unusual allele resulting from a single amino acid substitution and that the daf-21 null phenotype is early larval lethality. These results demonstrate that cGMP is a prominent second messenger in C. elegans chemosensory transduction and suggest a previously unknown role for Hsp90 in regulating cGMP levels.

Full Text

The Full Text of this article is available as a PDF (690.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Bargmann C. I., Hartwieg E., Horvitz H. R. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell. 1993 Aug 13;74(3):515–527. doi: 10.1016/0092-8674(93)80053-h. [DOI] [PubMed] [Google Scholar]
  3. Bargmann C. I., Horvitz H. R. Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron. 1991 Nov;7(5):729–742. doi: 10.1016/0896-6273(91)90276-6. [DOI] [PubMed] [Google Scholar]
  4. Bargmann C. I., Horvitz H. R. Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science. 1991 Mar 8;251(4998):1243–1246. doi: 10.1126/science.2006412. [DOI] [PubMed] [Google Scholar]
  5. Barnes W. M. PCR amplification of up to 35-kb DNA with high fidelity and high yield from lambda bacteriophage templates. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2216–2220. doi: 10.1073/pnas.91.6.2216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bloom L., Horvitz H. R. The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3414–3419. doi: 10.1073/pnas.94.7.3414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Borkovich K. A., Farrelly F. W., Finkelstein D. B., Taulien J., Lindquist S. hsp82 is an essential protein that is required in higher concentrations for growth of cells at higher temperatures. Mol Cell Biol. 1989 Sep;9(9):3919–3930. doi: 10.1128/mcb.9.9.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Buchner J. Hsp90 & Co. - a holding for folding. Trends Biochem Sci. 1999 Apr;24(4):136–141. doi: 10.1016/s0968-0004(99)01373-0. [DOI] [PubMed] [Google Scholar]
  10. C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
  11. Caplan A. J. Hsp90's secrets unfold: new insights from structural and functional studies. Trends Cell Biol. 1999 Jul;9(7):262–268. doi: 10.1016/s0962-8924(99)01580-9. [DOI] [PubMed] [Google Scholar]
  12. Chen C. F., Chen Y., Dai K., Chen P. L., Riley D. J., Lee W. H. A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock. Mol Cell Biol. 1996 Sep;16(9):4691–4699. doi: 10.1128/mcb.16.9.4691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chinkers M., Garbers D. L., Chang M. S., Lowe D. G., Chin H. M., Goeddel D. V., Schulz S. A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor. Nature. 1989 Mar 2;338(6210):78–83. doi: 10.1038/338078a0. [DOI] [PubMed] [Google Scholar]
  14. Chinkers M., Garbers D. L. The protein kinase domain of the ANP receptor is required for signaling. Science. 1989 Sep 22;245(4924):1392–1394. doi: 10.1126/science.2571188. [DOI] [PubMed] [Google Scholar]
  15. Chinkers M., Singh S., Garbers D. L. Adenine nucleotides are required for activation of rat atrial natriuretic peptide receptor/guanylyl cyclase expressed in a baculovirus system. J Biol Chem. 1991 Mar 5;266(7):4088–4093. [PubMed] [Google Scholar]
  16. Chinkers M. Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11075–11079. doi: 10.1073/pnas.91.23.11075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Coburn C. M., Bargmann C. I. A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans. Neuron. 1996 Oct;17(4):695–706. doi: 10.1016/s0896-6273(00)80201-9. [DOI] [PubMed] [Google Scholar]
  18. Coburn C. M., Mori I., Ohshima Y., Bargmann C. I. A cyclic nucleotide-gated channel inhibits sensory axon outgrowth in larval and adult Caenorhabditis elegans: a distinct pathway for maintenance of sensory axon structure. Development. 1998 Jan;125(2):249–258. doi: 10.1242/dev.125.2.249. [DOI] [PubMed] [Google Scholar]
  19. Cutforth T., Rubin G. M. Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinase in Drosophila. Cell. 1994 Jul 1;77(7):1027–1036. doi: 10.1016/0092-8674(94)90442-1. [DOI] [PubMed] [Google Scholar]
  20. Dalley B. K., Golomb M. Gene expression in the Caenorhabditis elegans dauer larva: developmental regulation of Hsp90 and other genes. Dev Biol. 1992 May;151(1):80–90. doi: 10.1016/0012-1606(92)90215-3. [DOI] [PubMed] [Google Scholar]
  21. Drewett J. G., Garbers D. L. The family of guanylyl cyclase receptors and their ligands. Endocr Rev. 1994 Apr;15(2):135–162. doi: 10.1210/edrv-15-2-135. [DOI] [PubMed] [Google Scholar]
  22. Estevez M., Attisano L., Wrana J. L., Albert P. S., Massagué J., Riddle D. L. The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature. 1993 Oct 14;365(6447):644–649. doi: 10.1038/365644a0. [DOI] [PubMed] [Google Scholar]
  23. Fesenko E. E., Kolesnikov S. S., Lyubarsky A. L. Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature. 1985 Jan 24;313(6000):310–313. doi: 10.1038/313310a0. [DOI] [PubMed] [Google Scholar]
  24. Freeman B. C., Morimoto R. I. The human cytosolic molecular chaperones hsp90, hsp70 (hsc70) and hdj-1 have distinct roles in recognition of a non-native protein and protein refolding. EMBO J. 1996 Jun 17;15(12):2969–2979. [PMC free article] [PubMed] [Google Scholar]
  25. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Georgi L. L., Albert P. S., Riddle D. L. daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase. Cell. 1990 May 18;61(4):635–645. doi: 10.1016/0092-8674(90)90475-t. [DOI] [PubMed] [Google Scholar]
  27. Golden J. W., Riddle D. L. The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. Dev Biol. 1984 Apr;102(2):368–378. doi: 10.1016/0012-1606(84)90201-x. [DOI] [PubMed] [Google Scholar]
  28. Gottlieb S., Ruvkun G. daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. Genetics. 1994 May;137(1):107–120. doi: 10.1093/genetics/137.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Grenert J. P., Johnson B. D., Toft D. O. The importance of ATP binding and hydrolysis by hsp90 in formation and function of protein heterocomplexes. J Biol Chem. 1999 Jun 18;274(25):17525–17533. doi: 10.1074/jbc.274.25.17525. [DOI] [PubMed] [Google Scholar]
  30. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  31. Horvitz H. R., Brenner S., Hodgkin J., Herman R. K. A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol Gen Genet. 1979 Sep;175(2):129–133. doi: 10.1007/BF00425528. [DOI] [PubMed] [Google Scholar]
  32. Huang L. S., Tzou P., Sternberg P. W. The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development. Mol Biol Cell. 1994 Apr;5(4):395–411. doi: 10.1091/mbc.5.4.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hurley J. B. Molecular properties of the cGMP cascade of vertebrate photoreceptors. Annu Rev Physiol. 1987;49:793–812. doi: 10.1146/annurev.ph.49.030187.004045. [DOI] [PubMed] [Google Scholar]
  34. Jakob U., Lilie H., Meyer I., Buchner J. Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo. J Biol Chem. 1995 Mar 31;270(13):7288–7294. doi: 10.1074/jbc.270.13.7288. [DOI] [PubMed] [Google Scholar]
  35. Kimura Y., Matsumoto S., Yahara I. Temperature-sensitive mutants of hsp82 of the budding yeast Saccharomyces cerevisiae. Mol Gen Genet. 1994 Mar;242(5):517–527. doi: 10.1007/BF00285275. [DOI] [PubMed] [Google Scholar]
  36. Komatsu H., Mori I., Rhee J. S., Akaike N., Ohshima Y. Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans. Neuron. 1996 Oct;17(4):707–718. doi: 10.1016/s0896-6273(00)80202-0. [DOI] [PubMed] [Google Scholar]
  37. Koutalos Y., Yau K. W. A rich complexity emerges in phototransduction. Curr Opin Neurobiol. 1993 Aug;3(4):513–519. doi: 10.1016/0959-4388(93)90049-5. [DOI] [PubMed] [Google Scholar]
  38. Liu L. X., Spoerke J. M., Mulligan E. L., Chen J., Reardon B., Westlund B., Sun L., Abel K., Armstrong B., Hardiman G. High-throughput isolation of Caenorhabditis elegans deletion mutants. Genome Res. 1999 Sep;9(9):859–867. doi: 10.1101/gr.9.9.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Malone E. A., Inoue T., Thomas J. H. Genetic analysis of the roles of daf-28 and age-1 in regulating Caenorhabditis elegans dauer formation. Genetics. 1996 Jul;143(3):1193–1205. doi: 10.1093/genetics/143.3.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mayer M. P., Bukau B. Molecular chaperones: the busy life of Hsp90. Curr Biol. 1999 May 6;9(9):R322–R325. doi: 10.1016/s0960-9822(99)80203-6. [DOI] [PubMed] [Google Scholar]
  41. Mazzarella R., Pengue G., Yoon J., Jones J., Schlessinger D. Differential expression of XAP5, a candidate disease gene. Genomics. 1997 Oct 1;45(1):216–219. doi: 10.1006/geno.1997.4912. [DOI] [PubMed] [Google Scholar]
  42. Miki N., Baraban J. M., Keirns J. J., Boyce J. J., Bitensky M. W. Purification and properties of the light-activated cyclic nucleotide phosphodiesterase of rod outer segments. J Biol Chem. 1975 Aug 25;250(16):6320–6327. [PubMed] [Google Scholar]
  43. Miller L. M., Plenefisch J. D., Casson L. P., Meyer B. J. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Cell. 1988 Oct 7;55(1):167–183. doi: 10.1016/0092-8674(88)90019-0. [DOI] [PubMed] [Google Scholar]
  44. Morris J. Z., Tissenbaum H. A., Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996 Aug 8;382(6591):536–539. doi: 10.1038/382536a0. [DOI] [PubMed] [Google Scholar]
  45. Nathan D. F., Vos M. H., Lindquist S. In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12949–12956. doi: 10.1073/pnas.94.24.12949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Obermann W. M., Sondermann H., Russo A. A., Pavletich N. P., Hartl F. U. In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol. 1998 Nov 16;143(4):901–910. doi: 10.1083/jcb.143.4.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Parkinson S. J., Carrithers S. L., Waldman S. A. Opposing adenine nucleotide-dependent pathways regulate guanylyl cyclase C in rat intestine. J Biol Chem. 1994 Sep 9;269(36):22683–22690. [PubMed] [Google Scholar]
  48. Picard D., Khursheed B., Garabedian M. J., Fortin M. G., Lindquist S., Yamamoto K. R. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature. 1990 Nov 8;348(6297):166–168. doi: 10.1038/348166a0. [DOI] [PubMed] [Google Scholar]
  49. Ren P., Lim C. S., Johnsen R., Albert P. S., Pilgrim D., Riddle D. L. Control of C. elegans larval development by neuronal expression of a TGF-beta homolog. Science. 1996 Nov 22;274(5291):1389–1391. doi: 10.1126/science.274.5291.1389. [DOI] [PubMed] [Google Scholar]
  50. Riddle D. L., Swanson M. M., Albert P. S. Interacting genes in nematode dauer larva formation. Nature. 1981 Apr 23;290(5808):668–671. doi: 10.1038/290668a0. [DOI] [PubMed] [Google Scholar]
  51. Scheibel T., Buchner J. The Hsp90 complex--a super-chaperone machine as a novel drug target. Biochem Pharmacol. 1998 Sep 15;56(6):675–682. doi: 10.1016/s0006-2952(98)00120-8. [DOI] [PubMed] [Google Scholar]
  52. Scheibel T., Siegmund H. I., Jaenicke R., Ganz P., Lilie H., Buchner J. The charged region of Hsp90 modulates the function of the N-terminal domain. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1297–1302. doi: 10.1073/pnas.96.4.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Scheibel T., Weikl T., Buchner J. Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1495–1499. doi: 10.1073/pnas.95.4.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Schumacher R. J., Hansen W. J., Freeman B. C., Alnemri E., Litwack G., Toft D. O. Cooperative action of Hsp70, Hsp90, and DnaJ proteins in protein renaturation. Biochemistry. 1996 Nov 26;35(47):14889–14898. doi: 10.1021/bi961825h. [DOI] [PubMed] [Google Scholar]
  55. Song H. Y., Dunbar J. D., Zhang Y. X., Guo D., Donner D. B. Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. J Biol Chem. 1995 Feb 24;270(8):3574–3581. [PubMed] [Google Scholar]
  56. Stebbins C. E., Russo A. A., Schneider C., Rosen N., Hartl F. U., Pavletich N. P. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell. 1997 Apr 18;89(2):239–250. doi: 10.1016/s0092-8674(00)80203-2. [DOI] [PubMed] [Google Scholar]
  57. Thomas J. H., Birnby D. A., Vowels J. J. Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics. 1993 Aug;134(4):1105–1117. doi: 10.1093/genetics/134.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Troemel E. R., Chou J. H., Dwyer N. D., Colbert H. A., Bargmann C. I. Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans. Cell. 1995 Oct 20;83(2):207–218. doi: 10.1016/0092-8674(95)90162-0. [DOI] [PubMed] [Google Scholar]
  59. Troemel E. R., Kimmel B. E., Bargmann C. I. Reprogramming chemotaxis responses: sensory neurons define olfactory preferences in C. elegans. Cell. 1997 Oct 17;91(2):161–169. doi: 10.1016/s0092-8674(00)80399-2. [DOI] [PubMed] [Google Scholar]
  60. Vaandrager A. B., Schulz S., De Jonge H. R., Garbers D. L. Guanylyl cyclase C is an N-linked glycoprotein receptor that accounts for multiple heat-stable enterotoxin-binding proteins in the intestine. J Biol Chem. 1993 Jan 25;268(3):2174–2179. [PubMed] [Google Scholar]
  61. Vaandrager A. B., van der Wiel E., de Jonge H. R. Heat-stable enterotoxin activation of immunopurified guanylyl cyclase C. Modulation by adenine nucleotides. J Biol Chem. 1993 Sep 15;268(26):19598–19603. [PubMed] [Google Scholar]
  62. Vowels J. J., Thomas J. H. Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis elegans. Genetics. 1994 Oct;138(2):303–316. doi: 10.1093/genetics/138.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Waterston R., Martin C., Craxton M., Huynh C., Coulson A., Hillier L., Durbin R., Green P., Shownkeen R., Halloran N. A survey of expressed genes in Caenorhabditis elegans. Nat Genet. 1992 May;1(2):114–123. doi: 10.1038/ng0592-114. [DOI] [PubMed] [Google Scholar]
  64. Wiech H., Buchner J., Zimmermann R., Jakob U. Hsp90 chaperones protein folding in vitro. Nature. 1992 Jul 9;358(6382):169–170. doi: 10.1038/358169a0. [DOI] [PubMed] [Google Scholar]
  65. Xu Y., Lindquist S. Heat-shock protein hsp90 governs the activity of pp60v-src kinase. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7074–7078. doi: 10.1073/pnas.90.15.7074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Xu Y., Singer M. A., Lindquist S. Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):109–114. doi: 10.1073/pnas.96.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Young J. C., Schneider C., Hartl F. U. In vitro evidence that hsp90 contains two independent chaperone sites. FEBS Lett. 1997 Nov 24;418(1-2):139–143. doi: 10.1016/s0014-5793(97)01363-x. [DOI] [PubMed] [Google Scholar]
  68. Yu S., Avery L., Baude E., Garbers D. L. Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3384–3387. doi: 10.1073/pnas.94.7.3384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Zwaal R. R., Broeks A., van Meurs J., Groenen J. T., Plasterk R. H. Target-selected gene inactivation in Caenorhabditis elegans by using a frozen transposon insertion mutant bank. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7431–7435. doi: 10.1073/pnas.90.16.7431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Zwaal R. R., Mendel J. E., Sternberg P. W., Plasterk R. H. Two neuronal G proteins are involved in chemosensation of the Caenorhabditis elegans Dauer-inducing pheromone. Genetics. 1997 Mar;145(3):715–727. doi: 10.1093/genetics/145.3.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. van der Keyl H., Kim H., Espey R., Oke C. V., Edwards M. K. Caenorhabditis elegans sqt-3 mutants have mutations in the col-1 collagen gene. Dev Dyn. 1994 Sep;201(1):86–94. doi: 10.1002/aja.1002010109. [DOI] [PubMed] [Google Scholar]
  72. van der Straten A., Rommel C., Dickson B., Hafen E. The heat shock protein 83 (Hsp83) is required for Raf-mediated signalling in Drosophila. EMBO J. 1997 Apr 15;16(8):1961–1969. doi: 10.1093/emboj/16.8.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES