Differentiation‐inducing factor 2 modulates chemotaxis via the histidine kinase DhkC‐dependent pathway in <i>Dictyostelium discoideum</i>

Kuwayama, Hidekazu; Kubohara, Yuzuru

doi:10.1002/1873-3468.12111

Cited by 4 publications

(11 citation statements)

References 42 publications

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“…Homologs of D. discoideum DhkB, which regulates spore germination and maintenance of spore dormancy (Zinda and Singleton 1998), and DhkC, which is required for the initiation of fruiting body formation (Singleton et al. 1998) and also affects chemotaxis (Kuwayama and Kubohara 2016), were also found in P. pallidum (fig. 4).…”

Section: Resultsmentioning

confidence: 99%

Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Kabbara

Hérivaux

Bernonville

et al. 2018

Genome Biology and Evolution

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Histidine kinases (HKs) are primary sensor proteins that act in cell signaling pathways generically referred to as “two-component systems” (TCSs). TCSs are among the most widely distributed transduction systems used by both prokaryotic and eukaryotic organisms to detect and respond to a broad range of environmental cues. The structure and distribution of HK proteins are now well documented in prokaryotes, but information is still fragmentary for eukaryotes. Here, we have taken advantage of recent genomic resources to explore the structural diversity and the phylogenetic distribution of HKs in the prominent eukaryotic supergroups. Searches of the genomes of 67 eukaryotic species spread evenly throughout the phylogenetic tree of life identified 748 predicted HK proteins. Independent phylogenetic analyses of predicted HK proteins were carried out for each of the major eukaryotic supergroups. This allowed most of the compiled sequences to be categorized into previously described HK groups. Beyond the phylogenetic analysis of eukaryotic HKs, this study revealed some interesting findings: 1) characterization of some previously undescribed eukaryotic HK groups with predicted functions putatively related to physiological traits; 2) discovery of HK groups that were previously believed to be restricted to a single kingdom in additional supergroups, and 3) indications that some evolutionary paths have led to the appearance, transfer, duplication, and loss of HK genes in some phylogenetic lineages. This study provides an unprecedented overview of the structure and distribution of HKs in the Eukaryota and represents a first step toward deciphering the evolution of TCS signaling in living organisms.

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Section: Resultsmentioning

confidence: 99%

Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Kabbara

Hérivaux

Bernonville

et al. 2018

Genome Biology and Evolution

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“…In addition to having differentiation-inducing activities, DIFs 1 and 2 at nanomolar levels function as modulators for Dictyostelium chemotactic cell movement toward cyclic adenosine monophosphate (cAMP) [48,49]. Importantly, the mechanisms for the modulation of chemotaxis by DIFs differ, at least in part, from those for the induction of stalk-cell differentiation [48,49,50]. Since the discovery of DIFs 1 and 2, the mechanisms underlying their functions have been examined [11,41,44,45,46,47,48,49,50,51,52,53,54,55,56,57] but remain to be fully elucidated; most importantly, their receptors have not been determined.…”

Section: Biological and Pharmacological Activities Of Dif-1 And Itmentioning

confidence: 99%

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Kubohara

Kikuchi

2018

Cells

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The cellular slime mold Dictyostelium discoideum is an excellent model organism for the study of cell and developmental biology because of its simple life cycle and ease of use. Recent findings suggest that Dictyostelium and possibly other genera of cellular slime molds, are potential sources of novel lead compounds for pharmacological and medical research. In this review, we present supporting evidence that cellular slime molds are an untapped source of lead compounds by examining the discovery and functions of polyketide differentiation-inducing factor-1, a compound that was originally isolated as an inducer of stalk-cell differentiation in D. discoideum and, together with its derivatives, is now a promising lead compound for drug discovery in several areas. We also review other novel compounds, including secondary metabolites, that have been isolated from cellular slime molds.

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“…We assume that DIF-1 has two receptors: DR1-D (DR-1 in Kuwayama et al, 2011) and DR1-C (DR-2 in Kuwayama et al, 2011); DIF-2 has one receptor, DR2-C (DR-3 in Kuwayama et al, 2011). We hypothesize that (1) DIF-1 induces stalk cell differentiation via DR1-D (DIF-1 receptor responsible for induction of cell differentiation) and an increase in cytosolic calcium and proton concentrations (Kubohara and Okamoto, 1994; Kubohara et al, 2007); (2) DIF-1 suppresses chemotactic cell movement in shallow cAMP gradients via DR1-C (DIF-1 receptor responsible for modulation of chemotaxis) and the GbpB-dependent pathway; and (3) DIF-2 promotes chemotactic cell movement in shallow cAMP gradients via DR2-C (DIF-2 receptor responsible for modulation of chemotaxis) and the Dictyostelium histidine kinase C (DhkC)-RegA-dependent pathway (Kuwayama and Kubohara, 2016, 2009; Kuwayama et al, 2011). DhkC might function as DR2-C (Kuwayama and Kubohara, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Chemotaxis toward cAMP was assessed by using Ax2 and gbpB – strains in the presence of additives as described previously (Kuwayama and Kubohara, 2009, 2016; Kuwayama et al, 2011). …”

Section: Methodsmentioning

confidence: 99%

“…In shallow cAMP gradients, DIF-1 inhibits chemotaxis via the phosphodiesterase GbpB, whereas DIF-2 stimulates chemotaxis via the phosphodiesterase RegA (Kuwayama and Kubohara, 2009; Kuwayama et al, 2011). The mechanisms by which DIFs modulate chemotaxis differ, at least in part, from those they use to induce stalk cell differentiation (Kuwayama and Kubohara, 2009, 2016; Kuwayama et al, 2011). Despite the importance of DIF-1 and DIF-2 in D. discoideum development, the entire signaling pathways they activate, including receptors, remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

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Evidence that differentiation-inducing factor-1 controls chemotaxis and cell differentiation, at least in part, via mitochondria inD. discoideum

et al. 2017

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Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum. However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization. DIF-1-BODIPY (5 µM) and DIF-1 (2 nM) induced stalk cell differentiation in the DIF-deficient strain HM44 in the presence of cyclic adenosine monosphosphate (cAMP), whereas DIF-1-NBD (5 µM) hardly induced stalk cell differentiation under the same conditions. Microscopic analyses revealed that the biologically active derivative, DIF-1-BODIPY, was incorporated by stalk cells at late stages of differentiation and was localized to mitochondria. The mitochondrial uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP), at 25–50 nM, and dinitrophenol (DNP), at 2.5–5 µM, induced partial stalk cell differentiation in HM44 in the presence of cAMP. DIF-1-BODIPY (1–2 µM) and DIF-1 (10 nM), as well as CCCP and DNP, suppressed chemotaxis in the wild-type strain Ax2 in shallow cAMP gradients. These results suggest that DIF-1-BODIPY and DIF-1 induce stalk cell differentiation and modulate chemotaxis, at least in part, by disturbing mitochondrial activity.

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Differentiation‐inducing factor 2 modulates chemotaxis via the histidine kinase DhkC‐dependent pathway in Dictyostelium discoideum

Cited by 4 publications

References 42 publications

Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Evidence that differentiation-inducing factor-1 controls chemotaxis and cell differentiation, at least in part, via mitochondria inD. discoideum

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