Culmination in dictyostelium is regulated by the cAMP-dependent protein kinase

Harwood, Adrian J.; Hopper, Neil A.; Simon, Marie‐Noëlle; Driscoll, Donna M.; Véron, Michel; Williams, Jeffrey

doi:10.1016/0092-8674(92)90225-2

Cited by 142 publications

(89 citation statements)

References 43 publications

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“…The cause of the block in stalk and spore differentiation by inhibition of PKA is obvious; here the transcription of prestalk and prespore specific genes is either completely absent or strongly reduced, or the transcripts are unstable [6,10,11]. It is less evident why PKA inhibition early in development should block the aggregation process and results obtained by different workers seem sometimes contradictory.…”

Section: Introductionmentioning

confidence: 77%

“…diseoideum strain AX3 was transformed by calcium-phosphate precipitation with vector pA15RM which harbours the actin6-NEO R selection cassette [12] and a gene fusion of the actinl 5 promoter directing expression of PKA-R subunit gene in which both cAMP binding sites where inactivated by site-directed mutagenesis yielding the mutant RM. Control cell lines (Rc) were transformed with vector pA15Rc which carries an additional mutation, that prevents interaction with the PKA-C subunit [5,6]. Transformants were selected for growth in the presence of 100 ¢tg/ml G418 in axenic medium.…”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

“…dominant-negative R subunits lacking cAMP binding sites (RM), or by disruption of the catalytic subunit (C) gene blocks cell aggregation and development [2][3][4][5]. When RM is overexpressed under either prestalk or prespore promoters, cells do not differentiate into stalk and spore cells respectively [6,7]. Conversely, constitutive activation of PKA either by overexpression of C subunits or by disruption of the R subunit gene, accelerates cell aggregation and induces precocious spore differentiation [8,9].…”

Section: Introductionmentioning

confidence: 99%

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cAMP‐dependent protein kinase activity is essential for preaggregative gene expression in Dictyostelium

Schulkes

Schaap

1995

FEBS Letters

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Section: Introductionmentioning

confidence: 77%

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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cAMP‐dependent protein kinase activity is essential for preaggregative gene expression in Dictyostelium

Schulkes

Schaap

1995

FEBS Letters

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“…However, folate can also stimulate adenylyl cyclase, which we have shown requires ERK2 activation. The physiological significance of folate-mediated ERK2 and adenylyl cyclase activity is probably not for the relay of cAMP but for the activation of cAMP-dependent protien kinase, which is required at multiple stages of the life cycle (41)(42)(43)(44)(45)(46)(47)(48)(49). Interestingly, a more primitive Dictyostelium species, D. minutum, exploits a folic acid-related compound as a chemoattractant in the aggregation stage, suggesting chemotaxis toward folic acid and other folate-mediated responses may be very ancient in this group of organisms (50).…”

Section: Discussionmentioning

confidence: 99%

Activation of the Mitogen-activated Protein Kinase ERK2 by the Chemoattractant Folic Acid in Dictyostelium

Maeda¹,

Firtel²

1997

Journal of Biological Chemistry

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In this study, we show that folic acid activates ERK2 in developmentally regulated manner and is required for ERK2 stimulation of adenylyl cyclase activity. Maximum levels of folate-stimulated ERK2 activity occur in cells from very early in development, prior to aggregation, and again at the tipped aggregate stages, corresponding to the stages in which folate receptors and the coupled G␣ subunit G␣4 are maximally expressed. During the activation by folic acid, ERK2 is phosphorylated on tyrosine residue(s) and contemporaneously shows a mobility shift on SDS-PAGE. Interestingly, this activation is not elicited in the absence of G␤ subunits, in contrast to the response to cAMP. This response also requires the G␣4 subunit known to be required for other folic acidmediated responses (Hadwiger, J., Lee, S., and Firtel, R. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10566 -10570). Furthermore, we show that the activation of ERK2 by cAMP is independent of the G␣4 subunit, while the activation of ERK2 by folate is independent of G␣2. Taken together, these data indicate that there are at least two pathways of ERK2 activation, heterotrimeric G proteindependent and -independent pathways. MAP 1 kinase cascades are used by eukaryotes to couple extracellular signals to diverse intracellular regulatory pathways. The diversity of these pathways is great and includes growth factor responses in mammalian cells, cell-type differentiation in Drosophila and Caenorhabditis elegans, mating and growth responses in yeast, and stress-mediated responses in yeast and mammalian cells. These cascades are mediated by various classes of G protein-and tyrosine kinase-coupled receptors (5-13). In Dictyostelium, three presumably independent MAP kinase cascades play essential regulatory roles during both growth and multicellular development. The MAP kinase kinase (MEK) DdMEK1 is required for chemotaxis toward cAMP during aggregation; ddmek1 null cells form very small aggregates but continue to differentiate into normally proportioned, but very small, fruiting bodies (14). DdMEK1 is specifically required at the time of cAMP stimulation for the activation of guanylyl cyclase and the production of cGMP, the second messenger for chemotaxis in these cells. Two MAP kinases, ERK1 and ERK2, have been identified and their functions characterized. ERK1 is required for vegetative growth and is thought to play roles during multicellular development (15), while ERK2 is required for the activation of adenylyl cyclase by the chemoattractant cAMP during aggregation, prespore-specific gene expression, and morphogenesis (2, 16). erk2 null cells are aggregation-deficient due to the inability to activate adenylyl cyclase and relay the cAMP signal but show normal activation of guanylyl cyclase, which couples to chemotaxis (17). erk2 null cells expressing a temperature-sensitive ERK2 show abnormal morphogenesis during the multicellular stages, as well as the inability to induce prespore gene expression when shifted to a nonpermissive temperature. ERK2 activity is induce ϳ...

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“…To identify components of the c-di-GMP signal transduction pathway, we first investigated mutants with a similar phenotype as the dgca− mutant. A mutant that expresses a dominant-negative inhibitor of PKA (PkaRm) from the ecmA prestalk promoter shows, like dgca−, prolonged slug migration, but eventually forms gnarled erect structures without stalk cells (14). We first tested whether c-di-GMP could restore proper fruiting body formation of the ecmA:: PkaRm slugs.…”

Section: C-di-gmp Regulation and Expression Patterns Of Putative C-dimentioning

confidence: 99%

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

Chen

Singh

Callebaut

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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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 cyclic diguanylate (c-di-GMP), synthesized by diguanylate cyclase A (DgcA), induces stalk formation. Here we 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 knockdown of cAMP-dependent protein kinase (PKA) activity in prestalk cells reduced stalk gene induction by c-di-GMP, whereas 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 pulses 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.

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Culmination in dictyostelium is regulated by the cAMP-dependent protein kinase

Cited by 142 publications

References 43 publications

cAMP‐dependent protein kinase activity is essential for preaggregative gene expression in Dictyostelium

cAMP‐dependent protein kinase activity is essential for preaggregative gene expression in Dictyostelium

Activation of the Mitogen-activated Protein Kinase ERK2 by the Chemoattractant Folic Acid in Dictyostelium

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

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