Showing papers by "Pauline Schaap published in 1993"

Extracellular cAMP is sufficient to restore developmental gene expression and morphogenesis in Dictyostelium cells lacking the aggregation adenylyl cyclase (ACA).

Abstract: Cell movement and cell-type-specific gene expression during Dictyostelium development are regulated by cAMP, which functions both as an extracellular hormone-like signal and an intracellular second messenger. Previous data indicated that aca- mutants, which lack adenylyl cyclase activity, fail to aggregate and do not express cell-type-specific genes. We show here that overexpression of ACG, a constitutively active adenylyl cyclase, which in wild-type cells is only expressed during spore germination, partially restores the coordination of cell movement and completely restores developmental gene expression. The aca- cells can also be induced to develop into viable spores by synergy with wild-type cells and, furthermore, form small but normal fruiting bodies, after a developmentally relevant regimen of stimulation with nanomolar cAMP pulses followed by micromolar cAMP concentrations. 2'-Deoxy cAMP, a cAMP analog that activates the cell-surface cAMP receptors but not cAMP-dependent protein kinase (PKA), also induces fruiting body formation as well as expression of prespore-specific and prestalk-enriched genes in aca- cells. Intracellular cAMP levels were not altered in aca- cells after stimulation with 2'-deoxy cAMP. Our data indicate that ACA is not required to provide intracellular cAMP for PKA activation but is essential to produce extracellular cAMP for coordination of cell movement during all stages of development and for induction of developmental gene expression.

A Pharmacological Approach to Identify Hormone Signaling Pathways Controlling Gene Regulation in Dictyostelium

Abstract: In Dictyostelium discoideum, extracellular cAMP functions as a hormone-like signal and induces chemotaxis and the expression of several classes of developmentally regulated genes. We describe a novel set of non-hydrolysable cAMP derivatives, which can selectively activate cell surface cAMP receptors (CAR) or the intracellular cAMP-dependent kinase (PKA), two putative target proteins for the effects of cAMP. Comparison of the affinities of these derivatives for CAR and PKA, to their efficacy as agonists for induction of three classes of cAMP-regulated genes, shows that CAR is the first target for cAMP regulation of gene expression.

Four signals to shape a slime mold

Abstract: The Dictyostelium life cycle is a fascinating example of the generation of highly ordered patterns of cell movement and tissue specification by a population of initially identical cells. Notably its spiral waves of chemotactic movement and the regulative aspects of its differentiation patterns have attracted considerable attention. Oscillatory cell movement was first visualized by Arndt (1937) in time lapse films, who compared this phenomenon to gusts of wind passing over a cornfield, transforming into rhythmic wave patterns emanating from a few dominant centers. The regulative capacity of Dictyosteliumslugs was demonstrated by a series of elegant experiments by Raper (1940), showing that dissected isolates from every part of a migrating slug would regulate to form a new slug and fruiting body. Bonner (1957) demonstrated that the proportion of stalk and spore cells in the fruiting body is practically independent of the total size of the organism over three orders of magnitude.