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Cyclic di-GMP Activates Adenylate Cyclase A and Protein Kinase A to Induce Stalk Formation in Dictyostelium

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Microbial Cyclic Di-Nucleotide Signaling

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Abstract

Cyclic di-GMP, an important prokaryote second messenger is used by the eukaryote Dictyostelium discoideum as a secreted signal to trigger stalk formation in fruiting bodies. Cyclic di-GMP is synthesized by a prokaryote-type diguanylate cyclase DgcA, but its mode of action was unknown. Transcriptional profiling yielded several target genes for cyclic di-GMP, which were tested for cyclic di-GMP induced expression in mutants with similar phenotypes as dgca-. A mutant with reduced PKA activity showed defective cyclic di-GMP induced stalk gene expression. Cyclic di-GMP increased cAMP levels in wild-type cells, but not in a mutant that lacked adenylate cyclase A (ACA) activity in slugs. This mutant also did not show cyclic di-GMP induced stalk gene expression. 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 the intermediate for cyclic di-GMP in normal development. ACA is expressed at the tip of emerging fruiting bodies, where it produces the cAMP pulses that organize morphogenetic movement. The tip is also the site where stalk differentiation initiates. Our finding that cyclic di-GMP acts on tip-expressed ACA explains why the Dictyostelium stalk is always formed at the morphogenetic organizer.

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Acknowledgment

Research reported in this study was funded by Leverhulme Trust grants RPG-2012-746 and RPG-2016-220, Wellcome Trust grant 100293/Z/12/Z and European Research Council grant 742288.

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Authors and Affiliations

  1. School of Life Sciences, University of Dundee, Dundee, UK

    Zhi-hui Chen, Christina Schilde & Pauline Schaap

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  1. Zhi-hui Chen
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  2. Christina Schilde
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  3. Pauline Schaap
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Correspondence to Pauline Schaap .

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Editors and Affiliations

  1. Institute of Biochemistry and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan

    Shan-Ho Chou

  2. Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile

    Nicolas Guiliani

  3. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA

    Vincent T. Lee

  4. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    Ute Römling

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Chen, Zh., Schilde, C., Schaap, P. (2020). Cyclic di-GMP Activates Adenylate Cyclase A and Protein Kinase A to Induce Stalk Formation in Dictyostelium . In: Chou, SH., Guiliani, N., Lee, V., Römling, U. (eds) Microbial Cyclic Di-Nucleotide Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-33308-9_32

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