Differential regulation of chemotaxis: Role of Gβγ in chemokine receptor-induced cell migration

Kerr, Jason S.; Jacques, Richard O.; Cardaba, Clara Moyano; Tse, T.; Sexton, Darren W.; Müeller, Anja

doi:10.1016/j.cellsig.2012.12.015

Cited by 9 publications

(10 citation statements)

References 46 publications

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“…Traditionally, it has been shown that CXCR4 activation leads to chemotaxis in a manner dependent on β ‐arrestin 2, ERK1/2 and G βγ and is PI3K dependent . Therefore, the implication of the dynamin PH domain in cell migration for CXCL12 is in line with the already published signalling networks, whereas the PH domain is not necessary for CCL3‐induced migration, as this migration is independent of PI3K activation . Overall, our study showed that there are distinct differences in signalling networks used by CC receptors compared with CXC receptors, which will yield novel therapeutic targets to prevent cell migration triggered by specific receptors.…”

Section: Discussionsupporting

confidence: 84%

“…Chambers were incubated at 37 °C and 5% CO 2 for 4 h before cells were counted. Data were analysed as previously described …”

Section: Methodsmentioning

confidence: 99%

“…10,12,13 Traditionally, it is thought that βγ-subunits of the G proteins induce migration via activation of phosphoinositide 3-kinase (PI3K); 14 however, we have recently shown that this seems not to be the case for CCL3-induced migration in THP-1 cells. 15 For CXCR4, it has been shown that migration under certain circumstances is dependent on β-arrestins as well as filamin A, a protein that can bind actin and interacts with β-arrestins. 16,17 This raises the possibility that β-arrestin-interacting and actin-interacting proteins are activated downstream of different types of chemokine receptors.…”

Section: Introductionmentioning

confidence: 99%

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Dynamin function is important for chemokine receptor‐induced cell migration

Jacques

Mills

Zerwes

et al. 2015

Cell Biochemistry & Function

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The HIV viral entry co-receptors CCR5 and CXCR4 function physiologically as typical chemokine receptors. Activation leads to cytosolic signal transduction that results in a variety of cellular responses such as cytoskeletal rearrangement and chemotaxis (CTX). Our aim was to investigate the signalling pathways involved in CC-and CXC-receptor mediated cell migration. Inhibition of dynamin I and II GTPase with dynasore completely inhibited CCL3 stimulated chemotaxis in THP-1 cells, whereas the dynasore analogue dyngo-4a, which is a more potent inhibitor, showed reduced ability to inhibit CC-chemokine induced CTX. In contrast, dynasore was not able to block cell migration via CXCR4. The same activation/inhibition pattern was verified in activated-T-lymphocytes for different CC-and CXC-chemokines. Cell migration induced by CC-and CXC-receptors is not relying on active internalisation processes driven by dynamin since the blockade of internalisation does not affect migration, but they might rely on dynamin interaction with the cytoskeleton. We identify here a functional difference in how CC-and CXC-receptor migration is controlled, suggesting that specific signalling networks are being employed for different receptor classes and potentially specific therapeutic targets to prevent receptor migration can be identified.

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Section: Discussionsupporting

confidence: 84%

“…Chambers were incubated at 37 °C and 5% CO 2 for 4 h before cells were counted. Data were analysed as previously described …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamin function is important for chemokine receptor‐induced cell migration

Jacques

Mills

Zerwes

et al. 2015

Cell Biochemistry & Function

Self Cite

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“…However, in contrast to traditional G-protein effectors Homer 3 binds both the GTP and GDP bound forms of Gα i2 . While GTP-Gα i likely has a limited role in chemokine receptor signaling, freed Gβγ subunits are known to activate several signaling pathways needed for gradient sensing and chemotaxis (20–23). An early consequence of the engagement of chemokine receptors is the acquisition of a polarized shape with the cell adopting a leading edge and a trailing uropod.…”

Section: Gi Proteinsmentioning

confidence: 99%

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

Kehrl

2016

Biochemical Pharmacology

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Leukocyte chemoattractant receptors are members of the G-protein coupled receptor (GPCR) family. Signaling downstream of these receptors directs the localization, positioning and homeostatic trafficking of leukocytes; as well as their recruitment to, and their retention at, inflammatory sites. Ligand induced changes in the molecular conformation of chemoattractant receptors results in the engagement of heterotrimeric G-proteins, which promotes α subunits to undergo GTP/GDP exchange. This results in the functionally release of βγ subunits from the heterotrimers, thereby activating downstream effector molecules, which initiate leukocyte polarization, gradient sensing, and directional migration. Pertussis toxin ADP ribosylates Gαi subunits and prevents chemoattractant receptors from triggering Gαi nucleotide exchange. The use of pertussis toxin revealed the essential importance of Gαi subunit nucleotide exchange for chemoattractant receptor signaling. More recent studies have identified a range of regulatory mechanisms that target these receptors and their associated heterotrimeric G-proteins, thereby helping to control the magnitude, kinetics, and duration of signaling. A failure in these regulatory pathways can lead to impaired receptor signaling and immunopathology. The analysis of mice with targeted deletions of Gαi isoforms as well as some of these G-protein regulatory proteins is providing insights into their roles in chemoattractant receptor signaling.

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“…C-X-C motif chemokine ligand 11 (CXCL11), released by immune cells during inflammation, is a small cytokine that may contribute to progression of colonic tumorigenesis (5). CXCL11 may regulate the chemotaxis of cells through interaction with a subset of 7-transmembrane, G protein-coupled receptors (6). In CRC, CXCL11 induces infiltration by tumor-associated macrophages and is associated with poor patient prognosis (7).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑144 mediates chronic inflammation and tumorigenesis in colorectal cancer progression via regulating C‑X‑C motif chemokine ligand 11

Han

Feng

Yu³

et al. 2018

Exp Ther Med

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Colorectal cancer (CRC) is one of the most common malignancies worldwide. The aim of the present study was to investigate the expression of microRNA-144 (miR-144) and C-X-C motif chemokine ligand 11 (CXCL11) in CRC and their association. Data from Gene Expression Omnibus (GEO) DataSets were analyzed to obtain the expression profile of CXCL11 in CRC. Subsequently, serum samples were collected from 65 subjects, including 39 patients with CRC and 26 controls; CRC and adjacent normal tissues were collected from all 39 CRC patients and the expression of CXCL11 was measured in these specimens. After searching for the potential regulator of CXCL11 through bioinformatics analysis, the levels of miR-144 in the clinical specimens were also detected. Finally, the regulatory association between miR-144 and CXCL11 was certified via the dual-luciferase reporter assay. Microarray data and bioinformatics analysis demonstrated that CXCL11 was significantly upregulated in CRC tissues and miR-144 was a potential regulator of CXCL11. In line with this finding, the expression of CXCL11 was significantly increased in the serum and tumor samples of patients with CRC, while that of miR-144 was downregulated. Dual-luciferase reporter assay revealed that miR-144 directly targets the 3′-untranslated region of CXCL11 mRNA to regulate its expression. These results demonstrated that enhanced CXCL11 expression in patients with CRC was associated with reduced miR-144 expression. The results of the present study may indicate a novel regulatory role of miR-144 in CRC through CXCL11 downregulation.

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Differential regulation of chemotaxis: Role of Gβγ in chemokine receptor-induced cell migration

Cited by 9 publications

References 46 publications

Dynamin function is important for chemokine receptor‐induced cell migration

Dynamin function is important for chemokine receptor‐induced cell migration

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

MicroRNA‑144 mediates chronic inflammation and tumorigenesis in colorectal cancer progression via regulating C‑X‑C motif chemokine ligand 11

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