title: Steroids initiate a signaling cascade that triggers rapid sporulation in Dictyostelium.
abstract: Encapsulation of prespore cells of Dictyostelium discoideum is controlled by several intercellular signals to ensure appropriate timing during fruiting body formation. Acyl-CoA-binding protein, AcbA, is secreted by prespore cells and processed by the prestalk protease TagC to form the 34 amino acid peptide SDF-2 that triggers rapid encapsulation. AcbA is secreted when gamma-aminobutyric acid (GABA) is released from prespore cells and binds to GrlE, a G protein-coupled receptor (GPCR). Analysis of SDF-2 production in mutant strains lacking Galpha subunits and GPCRs, either as pure populations or when mixed with other mutant strains, uncovered the non-cell-autonomous roles of GrlA, Galpha4 and Galpha7. We found that Galpha7 is essential for the response to GABA and is likely to be coupled to GrlE. GrlA-null and Galpha4-null cells respond normally to GABA but fail to secrete it. We found that they are necessary for the response to a small hydrophobic molecule, SDF-3, which is released late in culmination. Pharmacological inhibition of steroidogenesis during development blocked the production of SDF-3. Moreover, the response to SDF-3 could be blocked by the steroid antagonist mifepristone, whereas hydrocortisone and other steroids mimicked the effects of SDF-3 when added in the nanomolar range. It appears that SDF-3 is a steroid that elicits rapid release of GABA by acting through the GPCR GrlA, coupled to G protein containing the Galpha4 subunit. SDF-3 is at the head of the cascade that amplifies the signal for encapsulation to ensure the rapid, synchronous formation of spores.
authors.affiliation: Center for Molecular Genetics, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Anjard
authors.forename: Yongxuan
authors.initials: Y
authors.lastname: Su
authors.forename: William F
authors.initials: WF
authors.lastname: Loomis
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D026261:Diazepam Binding Inhibitor / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D033761:Spores, Protozoan / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013256:Steroids / Q000378:metabolism* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D017931:DNA Primers; D016054:DNA, Protozoan; D026261:Diazepam Binding Inhibitor; D044385:GTP-Binding Protein alpha Subunits; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D015800:Protozoan Proteins; D043562:Receptors, G-Protein-Coupled; C484455:SDF-2 protein, Dictyostelium discoideum; D013256:Steroids; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase