Folic acid stimulation of the Galpha4 G protein-mediated signal transduction pathway inhibits anterior prestalk cell development in Dictyostelium.
In Dictyostelium discoideum, several G proteins are known to mediate the transduction of signals that direct chemotactic movement and regulate developmental morphogenesis. The G protein alpha subunit encoded by the Galpha4 gene has been previously shown to be required for chemotactic responses to folic acid, proper developmental morphogenesis, and spore production. In this study, cells overexpressing the wild type Galpha4 gene, due to high copy gene dosage (Galpha4HC), were found to be defective in the ability to form the anterior prestalk cell region, express prespore- and prestalk-cell specific genes, and undergo spore formation. In chimeric organisms, Galpha4HC prespore cell-specific gene expression and spore production were rescued by the presence of wild-type cells, indicating that prespore cell development in Galpha4HC cells is limited by the absence of an intercellular signal. Transplanted wild-type tips were sufficient to rescue Galpha4HC prespore cell development, suggesting that the rescuing signal originates from the anterior prestalk cells. However, the deficiencies in prestalk-specific gene expression were not rescued in the chimeric organisms. Furthermore, Galpha4HC cells were localized to the prespore region of these chimeric organisms and completely excluded from the anterior prestalk region, suggesting that the Galpha4 subunit functions cell-autonomously to prevent anterior prestalk cell development. The presence of exogenous folic acid during vegetative growth and development delayed anterior prestalk cell development in wild-type but not galpha4 null mutant aggregates, indicating that folic acid can inhibit cell-type-specific differentiation by stimulation of the Galpha4-mediated signal transduction pathway. The results of this study suggest that Galpha4-mediated signals can regulate cell-type-specific differentiation by promoting prespore cell development and inhibiting anterior prestalk-cell development.
Hadwiger
J A
JA
Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater 74078-3020, USA. hadwige@okway.okstate.edu
Srinivasan
J
J
D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D002678:Chimera; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D005492:Folic Acid / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016254:Mutagenesis, Insertional; D015398:Signal Transduction / Q000187:drug effects*; D013170:Spores
D005492:Folic Acid; D000242:Cyclic AMP; D019204:GTP-Binding Proteins