Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 516-521 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences |
| Volume | 114 |
| Issue number | 3 |
| Early online date | 5 Jan 2017 |
| DOIs | |
| Publication status | Published - 17 Jan 2017 |
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Adenylate cyclase A acting on PKA mediates induction of stalk formation by cyclic diguanylate at the Dictyostelium organizer. / Chen, Zhi-Hui; Singh, Reema; Cole, Christian; Lawal, Hajara M.; Schilde, Christina; Febrer, Melanie; Barton, Geoffrey; Schaap, Pauline (Lead / Corresponding author).
In: Proceedings of the National Academy of Sciences, Vol. 114, No. 3, 17.01.2017, p. 516-521.Research output: Contribution to journal › Article
TY - JOUR
T1 - Adenylate cyclase A acting on PKA mediates induction of stalk formation by cyclic diguanylate at the Dictyostelium organizer
AU - Chen, Zhi-Hui
AU - Singh, Reema
AU - Cole, Christian
AU - Lawal, Hajara M.
AU - Schilde, Christina
AU - Febrer, Melanie
AU - Barton, Geoffrey
AU - Schaap, Pauline
N1 - This research was funded by Leverhulme Trust grant RPG-2012-746, BBSRC grant BB/K000799/1 and Wellcome Trust grant 100293/Z/12/Z.
PY - 2017/1/17
Y1 - 2017/1/17
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.1608393114
DO - 10.1073/pnas.1608393114
M3 - Article
VL - 114
SP - 516
EP - 521
JO - Proceedings of the National Academy of Sciences
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
IS - 3
ER -