Abstract
Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered. In the social amoeba Dictyostelium discoideum, c-di-GMP, produced by a prokaryote-type diguanylate cyclase, induces the differentiation of stalk cells, thereby enabling the formation of spore-bearing fruiting bodies. In this review, we summarize the currently known mechanisms that control the major life cycle transitions of Dictyostelium and focus particularly on the role of c-di-GMP in stalk formation. Stalk cell differentiation has characteristics of autophagic cell death, a process that also occurs in higher eukaryotes. We discuss the respective roles of c-di-GMP and of another signal molecule, differentiation-inducing factor 1, in autophagic cell death in vitro and in stalk formation in vivo.
Highlights
Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered
Especially c-di-GMP is believed to be the most commonly used signaling molecule in bacteria. c-diGMP very broadly mediates a range of cellular responses to environmental stimuli but has a prominent role in triggering the changes that cause bacteria to shift from a swarming planktonic state to a sessile biofilm-associated lifestyle [5, 6]
The social amoeba Dictyostelium discoideum was shown to use c-di-GMP as a secreted signal to induce stalk formation in its multicellular fruiting bodies [7]. Both c-di-GMP and the novel molecule 2=3=-cGAMP were found to activate the innate immune system by binding to STING. c-di-GMP enters mammalian cells through infection with bacteria, while 2=3=-cGAMP is endogenously produced by cGMP-AMP synthase in response to invasion with foreign DNA, which directly activates cGAS [8, 9]
Summary
Cyclic di-GMP (c-di-GMP) is currently recognized as the most widely used intracellular signal molecule in prokaryotes, but roles in eukaryotes were only recently discovered. In the social amoeba Dictyostelium discoideum, c-di-GMP, produced by a prokaryote-type diguanylate cyclase, induces the differentiation of stalk cells, thereby enabling the formation of spore-bearing fruiting bodies. The social amoeba Dictyostelium discoideum was shown to use c-di-GMP as a secreted signal to induce stalk formation in its multicellular fruiting bodies [7]. In mammals, both c-di-GMP and the novel molecule 2=3=-cGAMP were found to activate the innate immune system by binding to STING (stimulator of interferon genes). We summarize the processes leading to fruiting body formation and discuss the specific role of c-di-GMP in stalk cell differentiation
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