Activated cAMP receptors switch encystation into sporulation

Abstract

Metazoan embryogenesis is controlled by a limited number of signaling modules that are used repetitively at successive developmental stages. The development of social amoebas shows similar reiterated use of cAMP-mediated signaling. In the modelDictyostelium discoideum, secreted cAMP acting on 4 cAMP receptors (cARs1-4) coordinates cell movement during aggregation and fruiting body formation, and induces the expression of aggregation and sporulation genes at consecutive developmental stages. To identify hierarchy in the multiple roles of cAMP, we investigatedcARheterogeneity and function across the social amoeba phylogeny. The gene duplications that yieldedcARs 2-4occurred late in evolution. Many species have only acAR1ortholog that duplicated independently in the Polysphondylids and Acytostelids. Disruption of both cAR genes ofPolysphondylium pallidum(Ppal) did not affect aggregation, but caused complete collapse of fruiting body morphogenesis. The stunted structures contained disorganized stalk cells, which supported a mass of cysts instead of spores; cAMP triggered spore gene expression inPpal, but not in thecARnull mutant, explaining its sporulation defect. Encystation is the survival strategy of solitary amoebas, and lower taxa, likePpal, can still encyst as single cells. Recent findings showed that intracellular cAMP accumulation suffices to trigger encystation, whereas it is a complementary requirement for sporulation. Combined, the data suggest that cAMP signaling in social amoebas evolved from cAMP-mediated encystation in solitary amoebas; cAMP secretion in aggregates prompted the starving cells to form spores and not cysts, and additionally organized fruiting body morphogenesis. cAMP-mediated aggregation was the most recent innovation.