Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity DOI Creative Commons
Chun Zhou, Xia Chen, Rosa Planells‐Cases

et al.

Immunity, Journal Year: 2020, Volume and Issue: 52(5), P. 767 - 781.e6

Published: April 10, 2020

Language: Английский

Gasdermins: Effectors of Pyroptosis DOI

Stephen B. Kovacs,

Edward A. Miao

Trends in Cell Biology, Journal Year: 2017, Volume and Issue: 27(9), P. 673 - 684

Published: June 13, 2017

Language: Английский

Citations

1106

NLRP3 inflammasome activation and cell death DOI Open Access
Yi Huang, Wen Xu, Rongbin Zhou

et al.

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(9), P. 2114 - 2127

Published: July 28, 2021

Language: Английский

Citations

937

Programmed cell death as a defence against infection DOI
Ine Jørgensen,

Manira Rayamajhi,

Edward A. Miao

et al.

Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 17(3), P. 151 - 164

Published: Jan. 31, 2017

Language: Английский

Citations

911

Sgk1-Dependent Stimulation of Cardiac Na+/H+Exchanger Nhe1 by Dexamethasone DOI Creative Commons
Jakob Voelkl,

Venkanna Pasham,

Mohamed Siyabeldin E. Ahmed

et al.

Cellular Physiology and Biochemistry, Journal Year: 2013, Volume and Issue: 32(1), P. 25 - 38

Published: Jan. 1, 2013

Background/Aims: The serum- and glucocorticoid-inducible kinase Sgk1 contributes to cardiac remodeling development of heart failure, which is paralelled by Sgk1-dependent stimulation the Na+/H+ exchanger Nhe1. Glucocorticoids are powerful stimulators expression influence remodeling. present study thus explored whether glucocorticoid receptor agonist dexamethasone influenced expression, as well activity, phosphorylation at Ser703 Methods: Experiments were performed in HL-1 cardiomyocytes gene targeted mice lacking functional (sgk1-/-) respective wild type (sgk1+/+). Gene was determined quantitative RT-PCR Nhe1 utilizing a specific antibody against 14-3-3 binding motif P-Ser703, represents putative site recognition for involved activation. Cytosolic pH (pHi) 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence Nhe activity Na+-dependent realkalinization after an ammonium pulse. Results: Treatment with followed significant increase mRNA parallelled increased activity. Furthermore, significantly Spp1 expression. effects blunted cotreatment inhibitor EMD638683. Cotreatment cariporide similarly prevented dexamethasone-stimulated In sgk1+/+ mice, levels. but not sgk1-/- Ser703. Spp1, Ctgf, Nppa Nppb levels treated mice. Conclusions: critically activation

Language: Английский

Citations

847

The cytoplasm of living cells behaves as a poroelastic material DOI
Emad Moeendarbary, Léo Valon, Marco Fritzsche

et al.

Nature Materials, Journal Year: 2013, Volume and Issue: 12(3), P. 253 - 261

Published: Jan. 4, 2013

Language: Английский

Citations

615

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts DOI
Martin P. Stewart, Róbert Langer, Klavs F. Jensen

et al.

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(16), P. 7409 - 7531

Published: July 27, 2018

Intracellular delivery is a key step in biological research and has enabled decades of biomedical discoveries. It also becoming increasingly important industrial medical applications ranging from biomanufacture to cell-based therapies. Here, we review techniques for membrane disruption-based intracellular 1911 until the present. These methods achieve rapid, direct, universal almost any cargo molecule or material that can be dispersed solution. We start by covering motivations challenges associated with different types-small molecules, proteins/peptides, nucleic acids, synthetic nanomaterials, large cargo. The then presents broad comparison strategies followed an analysis disruption mechanisms biology cell response. cover mechanical, electrical, thermal, optical, chemical particular emphasis on their implementation. Throughout, highlight specific suggest areas need further experimentation. hope concepts discussed our inspire scientists engineers ideas improve delivery.

Language: Английский

Citations

596

Identification of LRRC8 Heteromers as an Essential Component of the Volume-Regulated Anion Channel VRAC DOI Open Access

Felizia K. Voss,

Florian Ullrich,

Jonas Münch

et al.

Science, Journal Year: 2014, Volume and Issue: 344(6184), P. 634 - 638

Published: April 11, 2014

One Swell Ion Channel When mammalian cells are faced with osmotic challenges, they need to swell or shrink. The molecular characterization of the volume-regulated anion channel (VRAC) remains unknown, although many candidate proteins have been proposed. Voss et al. (p. 634 , published online 10 April; see Perspective by Mindell ) used a genome-wide screen identify group leucine-rich repeat–containing (LRRC) necessary for forming VRAC. Suppression LRRC8A nearly eliminated presence VRAC in cells. A heterooligomer LRRC appears form Identification components is an essential step forward understanding swelling-activated ion channels and provides opportunities both mechanism its role physiology.

Language: Английский

Citations

576

The functional network of ion channels in T lymphocytes DOI
Michael D. Cahalan, K. George Chandy

Immunological Reviews, Journal Year: 2009, Volume and Issue: 231(1), P. 59 - 87

Published: Sept. 1, 2009

Summary: For more than 25 years, it has been widely appreciated that Ca 2+ influx is essential to trigger T‐lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers genetic manipulation have shown a unique contingent of ion channels orchestrates the initiation, intensity, duration signal. Five distinct types – Kv1.3, KCa3.1, Orai1+ stromal interacting molecule 1 (STIM1) [Ca ‐release activating (CRAC) channel], TRPM7, Cl swell comprise network performs functions vital for ongoing cellular homeostasis T‐cell activation, offering potential targets immunomodulation. Most recently, roles STIM1 Orai1 revealed in triggering forming CRAC channel following receptor engagement. STIM1, found cluster at immunological synapse contact with an antigen‐presenting cell; we discuss how might function modulate local signaling. Immuno‐imaging approaches are beginning shed light on vivo . Importantly, expression pattern K + hence can adapt depending upon state differentiation this allows different stages immune response be targeted specifically.

Language: Английский

Citations

566

SWELL1, a Plasma Membrane Protein, Is an Essential Component of Volume-Regulated Anion Channel DOI Creative Commons
Zhaozhu Qiu, Adrienne E. Dubin,

Jayanti Mathur

et al.

Cell, Journal Year: 2014, Volume and Issue: 157(2), P. 447 - 458

Published: April 1, 2014

Language: Английский

Citations

522

The chemistry, physiology and pathology of pH in cancer DOI Open Access
Pawel Swietach,

Richard D. Vaughan‐Jones,

Adrian L. Harris

et al.

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2014, Volume and Issue: 369(1638), P. 20130099 - 20130099

Published: Feb. 4, 2014

Cell survival is conditional on the maintenance of a favourable acid-base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously large fluxes, which would disturb pH if uncorrected. The cellular reservoir H(+)-binding sites can buffer changes but, its own, inadequate regulate intracellular pH. To stabilize at level, control trans-membrane traffic H(+)-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune extracellular ability change ionization state underlies exquisite sensitivity behaviour, including key processes in formation metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, adaptations H(+)/H(+)-equivalent transporters extracellular-facing CAs give means manipulate micro-environmental acidity, hallmark. Through genetic instability, apparatus for regulating sensing able adapt driving disease progression. therapeutic potential disturbing this sequence by targeting transporters, buffering or being investigated, monoclonal antibodies small-molecule inhibitors.

Language: Английский

Citations

490