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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

acrA  -  adenylate cyclase

Dictyostelium discoideum AX4

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High impact information on acrA

  • Adenylyl cyclase localization regulates streaming during chemotaxis [1].
  • Growth and development up to the slug stage are unaffected in acrA(-) mutant strains but the cells make almost no viable spores and produce unnaturally long stalks [2].
  • Investigations in Dictyostelium discoideum and neutrophils have established that pleckstrin homology (PH) domain-containing proteins that bind to the PI3K products PI(3,4)P2 and PI(3,4,5)P3, such as CRAC (cytosolic regulator of adenylyl cyclase) and Akt/PKB, translocate specifically to the leading edge of chemotaxing cells [3].
  • Yet, we previously isolated a constitutively active mutant of the Dictyostelium discoideum adenylyl cyclase harboring a single point mutation in the region linking the cytoplasmic and membrane domains (Leu-394) [4].
  • The ectopic expression of ACA from a constitutive promoter rescued the differentiation and morphogenesis of amiB- mutants [5].

Biological context of acrA

  • Our results indicate that mutations producing a stable "streamer" phenotype and reduced cyclic GMP phosphodiesterase activity are located in linkage group II, probably centromere distal to acrA [6].
  • 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 [7].
  • ACA produces intracellular and extracellular cAMP that drives further differentiation by inducing chemotaxis, developmental gene expression and morphogenesis of Dictyostelium cells [5].
  • Analyses of gene expression showed that amiB- cells fail to turn off the expression of one of the growth-phase genes, cprD, and to turn on the expression of ACA following starvation [5].
  • Although several genes have been identified as being essential for the initiation of differentiation process, such as the transcriptional activation of ACA expression, the molecular mechanisms of the growth/differentiation transition remain to be explored [5].

Anatomical context of acrA

  • The protein is thus involved in Ras/cAMP-dependent signal transduction and most likely serves as an adapter protein translocating the adenylyl cyclase complex to the actin cytoskeleton [8].
  • The N termini of CAPs play a role in Ras signaling and bind adenylyl cyclase; the C termini bind to G-actin and thereby alter the dynamic rearrangements of the microfilament system [9].
  • Based on the periodic regulation of adenylyl cyclase, cyclic AMP is released into the extracellular space in the form of pulses [10].

Associations of acrA with chemical compounds

  • The frequency of spontaneous methanol-resistant (acrA) mutants was approximately the same in cultures of radE and radE+ strains [11].

Analytical, diagnostic and therapeutic context of acrA

  • A genomewide microarray-assisted expression analysis combined with Northern blot analyses revealed a failure of CbfA-depleted cells to induce the gene encoding aggregation-specific adenylyl cyclase ACA and other genes required for cyclic AMP (cAMP) signal relay, which is necessary for aggregation and subsequent multicellular development [12].


  1. Adenylyl cyclase localization regulates streaming during chemotaxis. Kriebel, P.W., Barr, V.A., Parent, C.A. Cell (2003) [Pubmed]
  2. An adenylyl cyclase that functions during late development of Dictyostelium. Söderbom, F., Anjard, C., Iranfar, N., Fuller, D., Loomis, W.F. Development (1999) [Pubmed]
  3. The PI3K-mediated activation of CRAC independently regulates adenylyl cyclase activation and chemotaxis. Comer, F.I., Lippincott, C.K., Masbad, J.J., Parent, C.A. Curr. Biol. (2005) [Pubmed]
  4. Regulation of adenylyl cyclases by a region outside the minimally functional cytoplasmic domains. Parent, C.A., Borleis, J., Devreotes, P.N. J. Biol. Chem. (2002) [Pubmed]
  5. amiB, a novel gene required for the growth/differentiation transition in Dictyostelium. Kon, T., Adachi, H., Sutoh, K. Genes Cells (2000) [Pubmed]
  6. Genetic locus (stmF) associated with cyclic GMP phosphodiesterase activity in Dictyostelium discoideum maps in linkage group II. Coukell, M.B., Cameron, A.M. J. Bacteriol. (1985) [Pubmed]
  7. Delineation of the Roles Played by RasG and RasC in cAMP-dependent Signal Transduction during the Early Development of Dictyostelium discoideum. Bolourani, P., Spiegelman, G.B., Weeks, G. Mol. Biol. Cell (2006) [Pubmed]
  8. Crystallization of cyclase-associated protein from Dictyostelium discoideum. Hofmann, A., Hess, S., Noegel, A.A., Schleicher, M., Wlodawer, A. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
  9. Structure of the N-terminal domain of the adenylyl cyclase-associated protein (CAP) from Dictyostelium discoideum. Ksiazek, D., Brandstetter, H., Israel, L., Bourenkov, G.P., Katchalova, G., Janssen, K.P., Bartunik, H.D., Noegel, A.A., Schleicher, M., Holak, T.A. Structure (Camb.) (2003) [Pubmed]
  10. Adenylyl cyclase and the control of cell differentiation in Dictyostelium dicoideum. Roos, W., Malchow, D., Gerisch, G. Cell Differ. (1977) [Pubmed]
  11. radE, a new radiation-sensitive locus in Dictyostelium discoideum. Coukell, M.B., Cameron, A.M. J. Gen. Microbiol. (1979) [Pubmed]
  12. CbfA, the C-module DNA-binding factor, plays an essential role in the initiation of Dictyostelium discoideum development. Winckler, T., Iranfar, N., Beck, P., Jennes, I., Siol, O., Baik, U., Loomis, W.F., Dingermann, T. Eukaryotic Cell (2004) [Pubmed]
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