Delineation of the Roles Played by RasG and RasC in cAMP-dependent Signal Transduction during the Early Development of Dictyostelium discoideum

On starvation, the cellular slime mold Dictyostelium discoideum initiates a program of development leading to formation of multicellular structures. The initial cell aggregation requires chemotaxis to cyclic AMP (cAMP) and relay of the cAMP signal by the activation of adenylyl cyclase (ACA), and it has been shown previously that the Ras protein RasC is involved in both processes. Insertional inactivation of the rasG gene resulted in delayed aggregation and a partial inhibition of early gene expression, suggesting that RasG also has a role in early development. Both chemotaxis and ACA activation were reduced in the rasG cells, but the effect on chemotaxis was more pronounced. When the responses of rasG cells to cAMP were compared with the responses of rasC and rasC rasG strains, generated in otherwise isogenic backgrounds, these studies revealed that signal transduction through RasG is more important in chemotaxis and early gene expression, but that signal transduction through RasC is more important in ACA activation. Because the loss of either of the two Ras proteins alone did not result in a total loss of signal output down either of the branches of the cAMP signal-response pathway, there appears to be some overlap of function.

[1]  M. Khosla,et al.  The effect of the disruption of a gene encoding a PI4 kinase on the developmental defect exhibited by Dictyostelium rasC(-) cells. , 2005, Developmental biology.

[2]  C. Der,et al.  Signaling Interplay in Ras Superfamily Function , 2005, Current Biology.

[3]  Pablo A Iglesias,et al.  Chemoattractant signaling in dictyostelium discoideum. , 2004, Annual review of cell and developmental biology.

[4]  J. Colicelli,et al.  Human RAS Superfamily Proteins and Related GTPases , 2004, Science's STKE.

[5]  Jacqueline Cherfils,et al.  Structural principles for the multispecificity of small GTP-binding proteins. , 2004, Biochemistry.

[6]  G. Spiegelman,et al.  Chemoattractant‐induced Ras activation during Dictyostelium aggregation , 2004, EMBO reports.

[7]  William F. Loomis,et al.  RasC Plays a Role in Transduction of Temporal Gradient Information in the Cyclic-AMP Wave of Dictyostelium discoideum , 2004, Eukaryotic Cell.

[8]  F. McCormick,et al.  Signaling Specificity by Ras Family GTPases Is Determined by the Full Spectrum of Effectors They Regulate , 2004, Molecular and Cellular Biology.

[9]  Marten Postma,et al.  Chemotaxis: signalling modules join hands at front and tail , 2004, EMBO reports.

[10]  G. Spiegelman,et al.  Roles played by Ras subfamily proteins in the cell and developmental biology of microorganisms. , 2003, Cellular signalling.

[11]  P. Cosson,et al.  Dictyostelium discoideum transformation by oscillating electric field electroporation. , 2003, BioTechniques.

[12]  R. Firtel,et al.  Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of chemotaxing cells. , 2003, Molecular biology of the cell.

[13]  C. Herrmann Ras-effector interactions: after one decade. , 2003, Current opinion in structural biology.

[14]  P. Devreotes,et al.  Temporal and spatial regulation of chemotaxis. , 2002, Developmental cell.

[15]  Richard A. Firtel,et al.  Spatial and Temporal Regulation of 3-Phosphoinositides by PI 3-Kinase and PTEN Mediates Chemotaxis , 2002, Cell.

[16]  G. Spiegelman,et al.  RasC is required for optimal activation of adenylyl cyclase and Akt/PKB during aggregation , 2001, The EMBO journal.

[17]  R. Kessin Dictyostelium: Membranes and Organelles of Dictyostelium , 2001 .

[18]  R. Firtel,et al.  The molecular genetics of chemotaxis: sensing and responding to chemoattractant gradients , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[19]  M. Khosla,et al.  Functional overlap of the dictyostelium RasG, RasD and RasB proteins. , 2000, Journal of cell science.

[20]  R. Firtel,et al.  A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium. , 1999, Molecular biology of the cell.

[21]  Hui Ma,et al.  Chemoattractant‐mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium , 1999, The EMBO journal.

[22]  P. Devreotes,et al.  A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase in Dictyostelium. , 1997, Genes & development.

[23]  R. Insall,et al.  Dictyostelium RasG Is Required for Normal Motility and Cytokinesis, But Not Growth , 1997, The Journal of cell biology.

[24]  P. V. van Haastert,et al.  cGMP as second messenger during Dictyostelium chemotaxis , 1997, FEBS letters.

[25]  P. Devreotes,et al.  The aimless RasGEF is required for processing of chemotactic signals through G-protein-coupled receptors in Dictyostelium , 1996, Current Biology.

[26]  G. Shaulsky,et al.  CRAC, a cytosolic protein containing a pleckstrin homology domain, is required for receptor and G protein-mediated activation of adenylyl cyclase in Dictyostelium , 1994, The Journal of cell biology.

[27]  D. Cotter,et al.  RasG protein accumulation occurs just prior to amoebae emergence during spore germination in Dictyostelium discoideum. , 1994, FEMS microbiology letters.

[28]  Mark S. Boguski,et al.  Proteins regulating Ras and its relatives , 1993, Nature.

[29]  Frank McCormick,et al.  The GTPase superfamily: conserved structure and molecular mechanism , 1991, Nature.

[30]  J. Williams,et al.  Growing and developing Dictyostelium cells express different ras genes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[31]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[32]  P. Devreotes,et al.  Surface receptor-mediated activation of adenylate cyclase in Dictyostelium. Regulation by guanine nucleotides in wild-type cells and aggregation deficient mutants. , 1986, The Journal of biological chemistry.

[33]  P. V. Haastert A method for studying cAMP-relay in Dictyostelium discoideum: the effect of temperature on cAMP-relay , 1984 .

[34]  M. Brenner,et al.  Cyclic AMP levels and turnover during development of the cellular slime mold Dictyostelium discoideum. , 1978, Developmental biology.

[35]  J. Ashworth,et al.  Growth of myxameobae of the cellular slime mould Dictyostelium discoideum in axenic culture. , 1970, The Biochemical journal.

[36]  C. Parent,et al.  Molecular genetics of signal transduction in Dictyostelium. , 1996, Annual review of biochemistry.

[37]  R. Firtel,et al.  Analysis of G alpha 4, a G-protein subunit required for multicellular development in Dictyostelium. , 1992, Genes & development.

[38]  M. Sussman,et al.  Cultivation and synchronous morphogenesis of Dictyostelium under controlled experimental conditions. , 1987, Methods in cell biology.

[39]  C. A. Thomas,et al.  Molecular cloning. , 1977, Advances in pathobiology.