title: Non-autonomous regulation of a graded, PKA-mediated transcriptional activation signal for cell patterning.
abstract: The pseudoplasmodium or migrating slug of Dictyostelium is composed of non-terminally differentiated cells, organized along an anteroposterior axis. Cells in the anterior region of the slug define the prestalk compartment, whereas most of the posterior zone consists of prespore cells. We now present evidence that the cAMP-dependent protein kinase (PKA) and the RING domain/leucine zipper protein rZIP interact genetically to mediate a transcriptional activation gradient that regulates the differentiation of prespore cells within the posterior compartment of the slug. PKA is absolutely required for prespore differentiation. In contrast, rZIP negatively regulates prespore patterning; rzpA- cells, which lack rZIP, have reduced prestalk differentiation and a corresponding increase in prespore-specific gene expression. Using cell-specific markers and chimaeras of wild-type and rzpA- cells, we show that rZIP functions non-autonomously to establish a graded, prespore gene activation signal but autonomously to localize prespore expression. Overexpression of either the catalytic subunit or a dominant-negative regulatory subunit of PKA further demonstrates that PKA lies within the intracellular pathway that mediates the extracellular signal and regulates prespore patterning. Finally, we show that a 5'-distal segment within a prespore promoter that is responsive to a graded signal is also sensitive to PKA and rZIP, indicating that it acts directly at the level of prespore-specific gene transcription for regulation.
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK (MMDS; Bldg. 6/Bl-22), National Institutes of Health, Bethesda, MD 20892-2715, USA.
authors.forename: P
authors.initials: P
authors.lastname: Balint-Kurti
authors.forename: G T
authors.initials: GT
authors.lastname: Ginsburg
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: A R
authors.initials: AR
authors.lastname: Kimmel
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D019521:Body Patterning / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics; D002454:Cell Differentiation; D002678:Chimera / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D017125:Genes, Protozoan; D016350:Leucine Zippers; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction; D013170:Spores / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C105062:rZIP protein, Dictyostelium discoideum; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases