A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase in Dictyostelium

Genes Dev. 1997 Dec 1;11(23):3218-31. doi: 10.1101/gad.11.23.3218.


Genetic analysis was applied to identify novel genes involved in G protein-linked pathways controlling development. Using restriction enzyme-mediated integration (REMI), we have identified a new gene, Pianissimo (PiaA), involved in cAMP signaling in Dictyostelium discoideum. PiaA encodes a 130-kD cytosolic protein required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase. In piaA- null mutants, neither chemoattractant stimulation of intact cells nor GTPgammaS treatment of lysates activates the enzyme; constitutive expression of PiaA reverses these defects. Cytosols of wild-type cells that contain Pia protein reconstitute the GTPgammaS stimulation of adenylyl cyclase activity in piaA- lysates, indicating that Pia is directly involved in the activation. Pia and CRAC, a previously identified cytosolic regulator, are both essential for activation of the enzyme as lysates of crac- piaA- double mutants require both proteins for reconstitution. Homologs of PiaA are found in Saccharomyces cerevisiae and Schizosaccaromyces pombe; disruption of the S. cerevisiae homolog results in lethality. We propose that homologs of Pia and similar modes of regulation of these ubiquitous G protein-linked pathways are likely to exist in higher eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Chemotactic Factors / metabolism*
  • Chemotaxis
  • Cloning, Molecular
  • Cyclic GMP / biosynthesis
  • Cytosol / metabolism
  • Dictyostelium / enzymology
  • Dictyostelium / genetics
  • Dictyostelium / metabolism*
  • Enzyme Activation
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Gene Expression
  • Genes, Fungal
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Molecular Sequence Data
  • Protozoan Proteins*
  • Saccharomyces cerevisiae / genetics
  • Schizosaccharomyces / genetics
  • Sequence Homology, Amino Acid


  • Actins
  • Chemotactic Factors
  • Fungal Proteins
  • PiaA protein, Dictyostelium
  • Protozoan Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Cyclic GMP

Associated data

  • GENBANK/AF085194