Decoding the chemotactic signal

Thomas, Maria; Kleist, Andrew B.; Volkman, Brian F.

doi:10.1002/jlb.1mr0218-044

Cited by 22 publications

(15 citation statements)

References 160 publications

(302 reference statements)

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“…On the contrary, Grls, in particular grlA, G, H, and L are highly regulated (mostly repressed) in D. discoideum exposed to bacteria or folate. Remarkably, this short list includes the two receptors (grlG/far2 and grlL/far1) previously proposed to act as receptors for folate and bacterial LPS (Leiba et al, 2017;Pan et al, 2018;Thomas et al, 2018). It is common to observe down-regulation of a receptor upon engagement of its ligand as a means to down-regulate the cellular response.…”

Section: Discussionmentioning

confidence: 99%

“…We also analyzed the expression of glutamate receptor-like proteins, known as Grl proteins (Heidel et al, 2011). Grls are known to act as receptors for extracellular signals (Thomas et al, 2018), and grlG and grlL have been proposed to act as folate receptors and LPS (Pan et al, 2018;Thomas et al, 2018). We observed that the expression of 45.4% of these genes vary in particular grlA, G, H, and L (Figure 6 and Supplementary Table S4).…”

Section: Does Transcriptional Profiling Identify Genes Implicated In mentioning

confidence: 96%

“…At the molecular level, the D. discoideum genome encodes 61 putative G-protein-coupled receptors (GPCRs), including 17 γ-aminobutyric acid (GABA) or metabotropic glutamate receptor-like proteins, known as Grl (glutamate receptor-like) proteins (Heidel et al, 2011). GrlL and GrlG have recently been proposed to act as receptors allowing D. discoideum cells to respond to folic acid, which is released from bacteria (Pan et al, 2018;Thomas et al, 2018). D. discoideum amoebae do not have Toll-like receptors orthologs (Cosson and Soldati, 2008;Dunn et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional Responses of Dictyostelium discoideum Exposed to Different Classes of Bacteria

et al. 2020

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Dictyostelium discoideum amoebae feed by ingesting bacteria, then killing them in phagosomes. Ingestion and killing of different bacteria have been shown to rely on largely different molecular mechanisms. One would thus expect that D. discoideum adapts its ingestion and killing machinery when encountering different bacteria. In this study, we investigated by RNA sequencing if and how D. discoideum amoebae respond to the presence of different bacteria by modifying their gene expression patterns. Each bacterial species analyzed induced a specific modification of the transcriptome. Bacteria such as Bacillus subtilis, Klebsiella pneumoniae, or Mycobacterium marinum induced a specific and different transcriptional response, while Micrococcus luteus did not trigger a significant gene regulation. Although folate has been proposed to be one of the key molecules secreted by bacteria and recognized by hunting amoebae, it elicited a very specific and restricted transcriptional signature, distinct from that triggered by any bacteria analyzed here. Our results indicate that D. discoideum amoebae respond in a highly specific, almost non-overlapping manner to different species of bacteria. We additionally identify specific sets of genes that can be used as reporters of the response of D. discoideum to different bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Does Transcriptional Profiling Identify Genes Implicated In mentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Transcriptional Responses of Dictyostelium discoideum Exposed to Different Classes of Bacteria

et al. 2020

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“…The pathways promote actin polymerization and pseudopod formation at the side of the cell closest to the source of the extracellular cAMP, and induce myosin contraction at the 'back' of the cell to cause the cell to squeeze itself into the pseudopod. Guided in part by the Dictyostelium work, many workers have found that human neutrophils use very similar pathways and mechanisms (Thomas et al, 2018). Much of the current work in the chemotaxis field involves further elucidation of the pathways, their interactions, and how they regulate the cytoskeleton.…”

Section: Chemoattraction To Campmentioning

confidence: 99%

Extracellular signaling in Dictyostelium

Consalvo

Rijal²,

Tang³

et al. 2019

Int. J. Dev. Biol.

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In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other. The simplicity of Dictyostelium discoideum, and the wide variety of available tools to study this organism, makes it the equivalent of a hydrogen atom for cell and developmental biology. Studies using Dictyostelium have pioneered a good deal of our understanding of eukaryotic cell communication. In this review, we will present a brief overview of how Dictyostelium cells use extracellular signals to attract each other, repel each other, sense their local cell density, sense whether the nearby cells are starving or stressed, count themselves to organize the formation of structures containing a regulated number of cells, sense the volume they are in, and organize their multicellular development. Although we are probably just beginning to learn what the cells are telling each other, the elucidation of Dictyostelium extracellular signals has already led to the development of possible therapeutics for human diseases.

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“…Multicellular organisms orchestrate the migration of many cell types (1). In humans this essential function is carried out by the chemokine signaling network: a family of 46 secreted proteins that orchestrate directed cell migration through interactions with 23 chemokine receptive G protein-coupled receptors (GPCRs) (2).…”

Section: Introductionmentioning

confidence: 99%

The chemokine X-factor: Structure-function analysis of the CXC motif at CXCR4 and ACKR3

Wedemeyer

Mahn

Getschman

et al. 2020

Journal of Biological Chemistry

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The human chemokine family consists of 46 protein ligands that induce chemotactic cell migration by activating a family of 23 G protein-coupled receptors. The two major chemokine subfamilies, CC and CXC, bind distinct receptor subsets. A sequence motif defining these families, the X position in the CXC motif, is not predicted to make significant contacts with the receptor, but instead links structural elements associated with binding and activation. Here we use comparative analysis of chemokine NMR structures, structural modeling, and molecular dynamic simulations that suggested the X position reorients the chemokine N-terminus. Using CXCL12 as a model CXC chemokine, deletion of the X residue (P10) had little to no impact on the folded chemokine structure but diminished CXCR4 agonist activity as measured by ERK phosphorylation, chemotaxis, and Gi/o-mediated cAMP inhibition. Functional impairment was attributed to over 100-fold loss of CXCR4 binding affinity. Binding to the other CXCL12 receptor, ACKR3, was diminished nearly 500-fold. Deletion of P10 had little effect on CXCL12 binding to the CXCR4 N-terminus, a major component of the chemokine-GPCR interface. Replacement of the X residue with the most frequent amino acid at this position (P10Q) had an intermediate effect between wild-type and P10del in each assay, with ACKR3 having a higher tolerance for this mutation. This work shows that the X residue helps to position the CXCL12 N-terminus for optimal docking into the orthosteric pocket of CXCR4 and suggests that the CC/CXC motif contributes directly to receptor selectivity by orienting the chemokine N-terminus in a subfamily-specific direction.

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Decoding the chemotactic signal

Cited by 22 publications

References 160 publications

Transcriptional Responses of Dictyostelium discoideum Exposed to Different Classes of Bacteria

Transcriptional Responses of Dictyostelium discoideum Exposed to Different Classes of Bacteria

Extracellular signaling in Dictyostelium

The chemokine X-factor: Structure-function analysis of the CXC motif at CXCR4 and ACKR3

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