Adenylate cyclase A acting on PKA mediates induction of stalk formation by cyclic diguanylate at the Dictyostelium organizer

Zhi-Hui Chen, Reema Singh, Christian Cole, Hajara M. Lawal, Christina Schilde, Melanie Febrer, Geoffrey Barton, Pauline Schaap (Lead / Corresponding author)

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19 Citations (Scopus)
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Coordination of cell movement with cell differentiation is a major feat of embryonic development. The Dictyostelium stalk always forms at the organizing tip by a mechanism that is not understood. We previously reported that c-di-GMP, synthesized by diguanylate cyclase A (DgcA), induces stalk formation. We here used transcriptional profiling of dgca- structures to identify target genes for c-di-GMP, and used these genes to investigate the c-di-GMP signal transduction pathway. We found that knock-down of PKA activity in prestalk cells reduced stalk gene induction by c-di-GMP, while PKA activation bypassed the c-di-GMP requirement for stalk gene expression. c-di-GMP caused a persistent increase in cAMP, which still occurred in mutants lacking the adenylate cyclases ACG or ACR, or the cAMP phosphodiesterase RegA. However, both inhibition of adenylate cyclase A (ACA) with SQ22536, and incubation of a temperature-sensitive ACA mutant at the restrictive temperature prevented c-di-GMP induced cAMP synthesis as well as c-di-GMP induced stalk gene transcription. ACA produces the cAMP signals that coordinate Dictyostelium morphogenetic cell movement and is highly expressed at the organizing tip. The stalk-less dgca- mutant regained its stalk by expression of a light-activated adenylate cyclase from the ACA promoter and exposure to light, indicating that cAMP is also the intermediate for c-di-GMP in vivo. Our data show that the more widely expressed DgcA activates tip-expressed ACA, which then acts on PKA to induce stalk genes. These results explain why stalk formation in Dictyostelia always initiates at the site of the morphogenetic organizer.
Original languageEnglish
Pages (from-to)516-521
Number of pages6
JournalProceedings of the National Academy of Sciences
Issue number3
Early online date5 Jan 2017
Publication statusPublished - 17 Jan 2017


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