THE HISTIDINE KINASE DHKC REGULATES THE CHOICE BETWEEN MIGRATING SLUGS AND TERMINAL DIFFERENTIATION IN DICTYOSTELIUM-DISCOIDEUM

An early decision that a newly formed aggregate of Dictyostelium cells must make is whether to form a migrating slug or to proceed through c ulmination, the process of forming the mature fruiting body. The choic e between these alternative morphological pathways is influenced by ex ternal and internal cues. dhkC was identified as a potential hybrid se nsor kinase possessing domains homologous to the histidine kinase and receiver motifs of two-component signaling systems. Null strains of dh kC show a rapidly developing phenotype for aggregation through finger formation, and culmination commences immediately thereafter and procee ds at a normal rate to generate typical fruiting bodies. Ammonia, an e ndogenous 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. Convers ely, 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 source s 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 t o the integration of environmental and cellular signals so that the ap propriate choice is made between slug formation and culmination. We su ggest that DHKC may function as a sensor for ammonia, and that it is t he initial component of a phosphorelay signaling system that may modul ate the activity of cAMP-dependent protein kinase to either inhibit or promote culmination. Additionally, dhkC(-) spores were found to be de fective in germination, indicating a role for the DHKC signaling pathw ay in activating spore germination. (C) 1998 Academic Press.