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. 1992 Nov;3(11):1229–1234. doi: 10.1091/mbc.3.11.1229

Multiple cyclic AMP receptors are linked to adenylyl cyclase in Dictyostelium.

M Pupillo 1, R Insall 1, G S Pitt 1, P N Devreotes 1
PMCID: PMC275689  PMID: 1333842

Abstract

cAMP receptor 1 and G-protein alpha-subunit 2 null cell lines (car1- and g alpha 2-) were examined to assess the roles that these two proteins play in cAMP stimulated adenylyl cyclase activation in Dictyostelium. In intact wild-type cells, cAMP stimulation elicited a rapid activation of adenylyl cyclase that peaked in 1-2 min and subsided within 5 min; in g alpha 2- cells, this activation did not occur; in car1- cells an activation occurred but it rose and subsided more slowly. cAMP also induced a persistent activation of adenylyl cyclase in growth stage cells that contain only low levels of cAMP receptor 1 (cAR1). In lysates of untreated wild-type, car1-, or g alpha 2- cells, guanosine 5'-O-'(3-thiotriphosphate) (GTP gamma S) produced a similar 20-fold increase in adenylyl cyclase activity. Brief treatment of intact cells with cAMP reduced this activity by 75% in control and g alpha 2- cells but by only 8% in the car1- cells. These observations suggest several conclusions regarding the cAMP signal transduction system. 1) cAR1 and another cAMP receptor are linked to activation of adenylyl cyclase in intact cells. Both excitation signals require G alpha 2. 2) cAR1 is required for normal adaptation of adenylyl cyclase. The adaptation reaction caused by cAR1 is not mediated via G alpha 2. 3) Neither cAR1 nor G alpha 2 is required for GTP gamma S-stimulation of adenylyl cyclase in cell lysates. The adenylyl cyclase is directly coupled to an as yet unidentified G-protein.

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Selected References

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  1. Benovic J. L., Bouvier M., Caron M. G., Lefkowitz R. J. Regulation of adenylyl cyclase-coupled beta-adrenergic receptors. Annu Rev Cell Biol. 1988;4:405–428. doi: 10.1146/annurev.cb.04.110188.002201. [DOI] [PubMed] [Google Scholar]
  2. Devreotes P. Dictyostelium discoideum: a model system for cell-cell interactions in development. Science. 1989 Sep 8;245(4922):1054–1058. doi: 10.1126/science.2672337. [DOI] [PubMed] [Google Scholar]
  3. Dinauer M. C., Steck T. L., Devreotes P. N. Cyclic 3',5'-AMP relay in Dictyostelium discoideum V. Adaptation of the cAMP signaling response during cAMP stimulation. J Cell Biol. 1980 Aug;86(2):554–561. doi: 10.1083/jcb.86.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dohlman H. G., Thorner J., Caron M. G., Lefkowitz R. J. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem. 1991;60:653–688. doi: 10.1146/annurev.bi.60.070191.003253. [DOI] [PubMed] [Google Scholar]
  5. Federman A. D., Conklin B. R., Schrader K. A., Reed R. R., Bourne H. R. Hormonal stimulation of adenylyl cyclase through Gi-protein beta gamma subunits. Nature. 1992 Mar 12;356(6365):159–161. doi: 10.1038/356159a0. [DOI] [PubMed] [Google Scholar]
  6. Gilman A. G. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–649. doi: 10.1146/annurev.bi.56.070187.003151. [DOI] [PubMed] [Google Scholar]
  7. Kesbeke F., Snaar-Jagalska B. E., Van Haastert P. J. Signal transduction in Dictyostelium fgd A mutants with a defective interaction between surface cAMP receptors and a GTP-binding regulatory protein. J Cell Biol. 1988 Aug;107(2):521–528. doi: 10.1083/jcb.107.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Klein P. S., Sun T. J., Saxe C. L., 3rd, Kimmel A. R., Johnson R. L., Devreotes P. N. A chemoattractant receptor controls development in Dictyostelium discoideum. Science. 1988 Sep 16;241(4872):1467–1472. doi: 10.1126/science.3047871. [DOI] [PubMed] [Google Scholar]
  9. Kumagai A., Hadwiger J. A., Pupillo M., Firtel R. A. Molecular genetic analysis of two G alpha protein subunits in Dictyostelium. J Biol Chem. 1991 Jan 15;266(2):1220–1228. [PubMed] [Google Scholar]
  10. Kumagai A., Pupillo M., Gundersen R., Miake-Lye R., Devreotes P. N., Firtel R. A. Regulation and function of G alpha protein subunits in Dictyostelium. Cell. 1989 Apr 21;57(2):265–275. doi: 10.1016/0092-8674(89)90964-1. [DOI] [PubMed] [Google Scholar]
  11. Pitt G. S., Milona N., Borleis J., Lin K. C., Reed R. R., Devreotes P. N. Structurally distinct and stage-specific adenylyl cyclase genes play different roles in Dictyostelium development. Cell. 1992 Apr 17;69(2):305–315. doi: 10.1016/0092-8674(92)90411-5. [DOI] [PubMed] [Google Scholar]
  12. Pupillo M., Klein P., Vaughan R., Pitt G., Lilly P., Sun T., Devreotes P., Kumagai A., Firtel R. cAMP receptor and G-protein interactions control development in Dictyostelium. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):657–665. doi: 10.1101/sqb.1988.053.01.075. [DOI] [PubMed] [Google Scholar]
  13. Roos W., Malchow D., Gerisch G. Adenylyl cyclase and the control of cell differentiation in Dictyostelium dicoideum. Cell Differ. 1977 Oct;6(3-4):229–239. doi: 10.1016/0045-6039(77)90018-5. [DOI] [PubMed] [Google Scholar]
  14. Saxe C. L., 3rd, Johnson R., Devreotes P. N., Kimmel A. R. Multiple genes for cell surface cAMP receptors in Dictyostelium discoideum. Dev Genet. 1991;12(1-2):6–13. doi: 10.1002/dvg.1020120104. [DOI] [PubMed] [Google Scholar]
  15. Snaar-Jagalska B. E., Van Haastert P. J. Dictyostelium discoideum mutant synag 7 with altered G-protein-adenylate cyclase interaction. J Cell Sci. 1988 Oct;91(Pt 2):287–294. doi: 10.1242/jcs.91.2.287. [DOI] [PubMed] [Google Scholar]
  16. Sun T. J., Devreotes P. N. Gene targeting of the aggregation stage cAMP receptor cAR1 in Dictyostelium. Genes Dev. 1991 Apr;5(4):572–582. doi: 10.1101/gad.5.4.572. [DOI] [PubMed] [Google Scholar]
  17. Sun T. J., Van Haastert P. J., Devreotes P. N. Surface cAMP receptors mediate multiple responses during development in Dictyostelium: evidenced by antisense mutagenesis. J Cell Biol. 1990 May;110(5):1549–1554. doi: 10.1083/jcb.110.5.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tang W. J., Gilman A. G. Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits. Science. 1991 Dec 6;254(5037):1500–1503. doi: 10.1126/science.1962211. [DOI] [PubMed] [Google Scholar]
  19. Theibert A., Devreotes P. N. Surface receptor-mediated activation of adenylate cyclase in Dictyostelium. Regulation by guanine nucleotides in wild-type cells and aggregation deficient mutants. J Biol Chem. 1986 Nov 15;261(32):15121–15125. [PubMed] [Google Scholar]
  20. Vaughan R. A., Devreotes P. N. Ligand-induced phosphorylation of the cAMP receptor from Dictyostelium discoideum. J Biol Chem. 1988 Oct 5;263(28):14538–14543. [PubMed] [Google Scholar]
  21. Wu L. J., Devreotes P. N. Dictyostelium transiently expresses eight distinct G-protein alpha-subunits during its developmental program. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1141–1147. doi: 10.1016/0006-291x(91)91690-e. [DOI] [PubMed] [Google Scholar]

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