Functional interaction between TRP4 and CFTR in mouse aorta endothelial cells

Lin, Wei Che; Freichel, Marc; Jaspers, Martine; Cuppens, Harry; Cassiman, Jean‐Jacques; Droogmans, Guy; Flockerzi, Veit; Nilius, Bernd

doi:10.1186/1472-6793-1-3

Cited by 20 publications

(4 citation statements)

References 34 publications

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“…Among others, one possible hypothesis is that TRP channels constitute a missing link between the abnormal Ca 2+ levels observed in CF cells and CFTR dysfunction. Indeed, TRPC4 may interact more directly with CFTR by forming a signaling complex via binding of their PDZ-binding motifs to PDZ-domain proteins 45 . It is therefore tempting to speculate that TRPs might be either regulators of CFTR or targets of CFTR regulating proteins.…”

Section: Discussionmentioning

confidence: 99%

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis

Lévêque

Penna

Trionnaire

et al. 2018

Sci Rep

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Whereas many phagocytosis steps involve ionic fluxes, the underlying ion channels remain poorly defined. As reported in mice, the calcium conducting TRPV2 channel impacts the phagocytic process. Macrophage phagocytosis is critical for defense against pathogens. In cystic fibrosis (CF), macrophages have lost their capacity to act as suppressor cells and thus play a significant role in the initiating stages leading to chronic inflammation/infection. In a previous study, we demonstrated that impaired function of CF macrophages is due to a deficient phagocytosis. The aim of the present study was to investigate TRPV2 role in the phagocytosis capacity of healthy primary human macrophage by studying its activity, its membrane localization and its recruitment in lipid rafts. In primary human macrophages, we showed that P. aeruginosa recruits TRPV2 channels at the cell surface and induced a calcium influx required for bacterial phagocytosis. We presently demonstrate that to be functional and play a role in phagocytosis, TRPV2 might require a preferential localization in lipid rafts. Furthermore, CF macrophage displays a perturbed calcium homeostasis due to a defect in TRPV2. In this context, deregulated TRPV2-signaling in CF macrophages could explain their defective phagocytosis capacity that contribute to the maintenance of chronic infection.

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Section: Discussionmentioning

confidence: 99%

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis

Lévêque

Penna

Trionnaire

et al. 2018

Sci Rep

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“…This method is described in detail elsewhere (12,13). These cells express TRP12 as previously shown with Northern blot analysis (8).…”

Section: Cell Culture Hvrl-2 Stable Cell Line (Hvrl-21321n1)-atmentioning

confidence: 99%

Activation of TRPV4 Channels (hVRL-2/mTRP12) by Phorbol Derivatives

Watanabe¹,

Davis²,

Smart³

et al. 2002

Journal of Biological Chemistry

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536

469

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We have studied activation by phorbol derivatives of TRPV4 channels, the human VRL-2, and murine TRP12 channels, which are highly homologous to the human VR-OAC, and the human and murine OTRPC4 channel. ] i inhibits the channel with an IC 50 of 406 nM. Ruthenium Red at a concentration of 1 M completely blocks inward currents at ؊80 mV but has a smaller effect on outward currents likely indicating a voltage dependent channel block. We concluded that the phorbol derivatives activate TRPV4 (VR-OAC, VRL-2, OTRPC4, TRP12) independently from protein kinase C, in a manner consistent with direct agonist gating of the channel.

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“…[8][9][10] It is primarily localized to the luminal, or apical, membranes of epithelial cells in several functionally diverse tissues including the airway, intestine, pancreas, kidney, vas deferens, and sweat duct. As its name implies, in addition to functioning as a secretory Cl À channel, CFTR also acts as a regulator exerting modulatory influences over a wide variety of other ion channels, transporters, and processes, such as the epithelial Na + channel (ENaC), [11][12][13] the outwardly rectifying chloride channel, [14][15][16] apical K + channels from renal epithelial cell ROMKs, [17][18][19][20][21] Ca 2+ -activated Cl À channels, 22,23 aquaporin water channels, [24][25][26] Cl À /HCO 3 À exchangers, [27][28][29][30][31] sodiumbicarbonate transporters, [32][33][34] Na + /H + exchangers, 34,35 and ATP release mechanisms. 36,37 CFTR is involved in two major diseases: cystic fibrosis and secretory diarrhea…”

Section: Introductionmentioning

confidence: 99%

CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners

2010

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The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel located primarily at the apical or luminal surfaces of epithelial cells in the airway, intestine, pancreas, kidney, sweat gland, as well as male reproductive tract, where it plays a crucial role in transepithelial fluid homeostasis. CFTR dysfunction can be detrimental and may result in life-threatening disorders. CFTR hypofunctioning because of genetic defects leads to cystic fibrosis, the most common lethal genetic disease in Caucasians, whereas CFTR hyperfunctioning resulting from various infections evokes secretory diarrhea, the leading cause of mortality in early childhood. Therefore, maintaining a dynamic balance between CFTR up-regulating processes and CFTR down-regulating processes is essential for maintaining fluid and body homeostasis. Accumulating evidence suggests that protein-protein interactions play a critical role in the finetuned regulation of CFTR function. A growing number of proteins have been reported to interact directly or indirectly with CFTR chloride channel, suggesting that CFTR might be coupled spatially and temporally to a wide variety of interacting partners including ion channels, receptors, transporters, scaffolding proteins, enzyme molecules, signaling molecules, and effectors. Most interactions occur primarily between the opposing terminal tails (amino or carboxyl) of CFTR protein and its binding partners, either directly or mediated through various PDZ scaffolding proteins. These dynamic interactions impact the channel function, as well as localization and processing of CFTR protein within cells. This article reviews the most recent progress and findings about the interactions between CFTR and its binding partners through PDZ scaffolding proteins, as well as the spatiotemporal regulation of CFTR-containing macromolecular signaling complexes in the apical compartments of polarized cells lining the secretory epithelia.

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Functional interaction between TRP4 and CFTR in mouse aorta endothelial cells

Abstract: Background: This study describes the functional interaction between the putative Ca 2+ channel

Cited by 20 publications

References 34 publications

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis

Activation of TRPV4 Channels (hVRL-2/mTRP12) by Phorbol Derivatives

CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners

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