Spatial distribution and activity of Na + /K + -ATPase in lipid bilayer membranes with phase boundaries

Bhatia, Tripta; Cornelius, Flemming; Brewer, Jonathan R.; Bagatolli, Luís A.; Simonsen, Adam Cohen; Ipsen, John Hjort; Mouritsen, Ole G.

doi:10.1016/j.bbamem.2016.03.015

Cited by 39 publications

(27 citation statements)

References 45 publications

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“…Sorting and activation of membrane proteins is the most studied function of lipid domains [54][55][56][57]. These effects can be attributed either to the modification of bilayer properties (thickness, curvature or surface tension) or to the binding of specific lipids to the protein surface.…”

Section: Lipid Domains As Modulators Of Piezo1 and Pmca Membrane Locamentioning

confidence: 99%

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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Background/Aims: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Methods: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Results: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Conclusion: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated.

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Section: Lipid Domains As Modulators Of Piezo1 and Pmca Membrane Locamentioning

confidence: 99%

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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“…Such binding is mostly expected to hinder proper motions of the transmembrane helices by impairing specific protein-lipid interactions. This may explain the experimentally observed inhibition of Na + /K + -ATPase by CsA given that the Na + /K + -ATPase (i) undergoes large-scale conformational changes during its reaction cycle and (ii) its activity is strongly dependent of the membrane environment (Bhatia et al, 2016).…”

Section: Discussionmentioning

confidence: 86%

Cyclosporine A inhibits MRTF-SRF signalling through Na⁺/K⁺ ATPase inhibition & Actin remodelling

Burat

Faucher

Čechová

et al. 2018

Preprint

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Calcineurin Inhibitors (CNI) are the pillars of immunosuppression in transplantation.However, they display a potent nephrotoxicity whose mechanisms remained widely unsolved. We used an untargeted quantitative proteomic approach (iTRAQ technology) to highlight new targets of CNI in renal proximal tubular cells (RPTCs). CNI-treated RPTCs proteome displayed an over-representation of Actin-binding proteins with a CNI-specific expression profile. Cyclosporine A (CsA) induced F-Actin remodelling and depolymerisation, decreased F-Actin-stabilizing, polymerization-promoting Cofilin (CFL) oligomers and inhibited the G-Actin-regulated serum responsive factor (SRF) pathway. Inhibition of CFL canonical phosphorylation pathway reproduced CsA effects; however, Ser3, an analogue of the phosphorylation site of CFL prevented the effects of CsA which suggests that CsA acted independently from the canonical CFL regulation. CFL is known to be regulated by the Na + /K + -ATPase. Molecular docking calculations evidenced 2 inhibiting sites of CsA on Na + /K + -ATPase and a 23% decrease in Na + /K + -ATPase activity of RPTCs was observed with CsA. Ouabain, a specific inhibitor of Na + /K + -ATPase also reproduced CsA effects on Actin organization and SRF activity. Altogether, these results described a new original pathway explaining CsA nephrotoxicity.

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“…This may explain the experimentally observed inhibition of Na + /K + -ATPase by CsA given that the Na + /K + -ATPase (a) undergoes large-scale conformational changes during its reaction cycle; and (b) its activity is strongly dependent of the membrane environment. 70 Interestingly, in the open structure, there are no binding sites in the transmembrane region, but there are two at the membrane interface that could (a) impair domain motions; and (b) prevent the proper closing of N-and A-domains during the reaction cycle. It is noteworthy that there is also a binding site under the A-domain, similar to the one in the closed conformation.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine A inhibits MRTF‐SRF signaling through Na ⁺ /K ⁺ ATPase inhibition and actin remodeling

et al. 2019

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Calcineurin inhibitors (CNI) are the pillars of immunosuppression in transplantation. However, they display a potent nephrotoxicity whose mechanisms remained widely unsolved. We used an untargeted quantitative proteomic approach (iTRAQ technology) to highlight new targets of CNI in renal proximal tubular cells (RPTCs). CNI‐treated RPTCs proteome displayed an over‐representation of actin‐binding proteins with a CNI‐specific expression profile. Cyclosporine A (CsA) induced F‐actin remodeling and depolymerization, decreased F‐actin‐stabilizing, polymerization‐promoting cofilin (CFL) oligomers, and inhibited the G‐actin‐regulated serum response factor (SRF) pathway. Inhibition of CFL canonical phosphorylation pathway reproduced CsA effects; however, S3‐R, an analogue of the phosphorylation site of CFL prevented the effects of CsA which suggests that CsA acted independently from the canonical CFL regulation. CFL is known to be regulated by the Na+/K+‐ATPase. Molecular docking calculations identified two inhibiting sites of CsA on Na+/K+‐ATPase and a 23% decrease in Na+/K+‐ATPase activity of RPTCs was observed with CsA. Ouabain, a specific inhibitor of Na+/K+‐ATPase also reproduced CsA effects on actin organization and SRF activity. Altogether, these results described a new original pathway explaining CsA nephrotoxicity.

show abstract

Spatial distribution and activity of Na + /K + -ATPase in lipid bilayer membranes with phase boundaries

Cited by 39 publications

References 45 publications

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Cyclosporine A inhibits MRTF-SRF signalling through Na⁺/K⁺ ATPase inhibition & Actin remodelling

Cyclosporine A inhibits MRTF‐SRF signaling through Na ⁺ /K ⁺ ATPase inhibition and actin remodeling

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Spatial distribution and activity of Na + /K + -ATPase in lipid bilayer membranes with phase boundaries

Cited by 39 publications

References 45 publications

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Cyclosporine A inhibits MRTF-SRF signalling through Na+/K+ ATPase inhibition & Actin remodelling

Cyclosporine A inhibits MRTF‐SRF signaling through Na + /K + ATPase inhibition and actin remodeling

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Product

Resources

About

Cyclosporine A inhibits MRTF-SRF signalling through Na⁺/K⁺ ATPase inhibition & Actin remodelling

Cyclosporine A inhibits MRTF‐SRF signaling through Na ⁺ /K ⁺ ATPase inhibition and actin remodeling