title: The histidine kinase dhkC regulates the choice between migrating slugs and terminal differentiation in Dictyostelium discoideum.
abstract: An early decision that a newly formed aggregate of Dictyostelium cells must make is whether to form a migrating slug or to proceed through culmination, the process of forming the mature fruiting body. The choice between these alternative morphological pathways is influenced by external and internal cues. dhkC was identified as a potential hybrid sensor kinase possessing domains homologous to the histidine kinase and receiver motifs of two-component signaling systems. Null strains of dhkC show a rapidly developing phenotype for aggregation through finger formation, and culmination commences immediately thereafter and proceeds at a normal rate to generate typical fruiting bodies. Ammonia, an endogenous regulator of the slug versus culmination choice, results in a prolonged slug stage for wild-type strains while the dhkC- strain bypasses the slug stage in the presence or absence of ammonia. Conversely, expression in wild-type cells of a modified DHKC protein composed of only the histidine kinase domain results in normal timing through early aggregation, but subsequent development is significantly delayed. The resulting fingers, once formed, readily convert to slugs that do not undergo culmination but instead migrate until their energy sources are depleted. The slugger phenotype is dependent on the presence of a functional response regulator REGA, and it is rescued by exogenously supplied cAMP. Together, the results indicate that DHKC contributes to the integration of environmental and cellular signals so that the appropriate choice is made between slug formation and culmination. We suggest that DHKC may function as a sensor for ammonia, and that it is the initial component of a phosphorelay signaling system that may modulate the activity of cAMP-dependent protein kinase to either inhibit or promote culmination. Additionally, dhkC- spores were found to be defective in germination, indicating a role for the DHKC signaling pathway in activating spore germination.
authors.affiliation: Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee, 37235, USA. charles.k.singleton@vanderbilt.edu
authors.forename: C K
authors.initials: CK
authors.lastname: Singleton
authors.forename: M J
authors.initials: MJ
authors.lastname: Zinda
authors.forename: B
authors.initials: B
authors.lastname: Mykytka
authors.forename: P
authors.initials: P
authors.lastname: Yang
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D004023:Dictyostelium / Q000201:enzymology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics; D000071677:Histidine Kinase; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D015800:Protozoan Proteins; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015800:Protozoan Proteins; D012333:RNA, Messenger; D000641:Ammonia; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D000071677:Histidine Kinase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C112742:regA protein, Dictyostelium