Extracellular Nucleotides and P2 Receptors in Renal Function DOI Open Access
Volker Vallon, Robert J. Unwin,

Edward W. Inscho

et al.

Physiological Reviews, Journal Year: 2019, Volume and Issue: 100(1), P. 211 - 269

Published: Aug. 22, 2019

The understanding of the nucleotide/P2 receptor system in regulation renal hemodynamics and transport function has grown exponentially over last 20 yr. This review attempts to integrate available data while also identifying areas missing information. First, determinants nucleotide concentrations interstitial tubular fluids kidney are described, including mechanisms cellular release nucleotides their extracellular breakdown. Then cell membrane expression P2X P2Y receptors is discussed context effects on vascular functions. Attention paid cortical vasculature intraglomerular structures, autoregulation blood flow, tubuloglomerular feedback, control medullary flow. role autocrine/paracrine sodium fluid collecting duct outlined together with its integrative homeostasis pressure control. final section summarizes rapidly growing evidence indicating a prominent pathophysiology aims identify potential therapeutic opportunities, hypertension, lithium-induced nephropathy, polycystic disease, inflammation. We only beginning unravel distinct physiological pathophysiological influences associated perspectives.

Language: Английский

CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease DOI Open Access
Thomas J. Jentsch, Michael Pusch

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(3), P. 1493 - 1590

Published: May 31, 2018

CLC anion transporters are found in all phyla and form a gene family of eight members mammals. Two proteins, each which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory β-subunits for function. proteins come two flavors: channels anion/proton exchangers. Structures these protein classes surprisingly similar. Extensive structure-function analysis identified residues involved permeation, anion-proton coupling gating led attractive biophysical models. In mammals, ClC-1, -2, -Ka/-Kb plasma membrane Cl − channels, whereas ClC-3 through ClC-7 2Cl /H + -exchangers endolysosomal membranes. Biological roles CLCs were mostly studied but also plants model organisms like yeast Caenorhabditis elegans. have the control electrical excitability, extra- intracellular homeostasis, transepithelial transport, exchangers influence vesicular composition impinge on endocytosis lysosomal The diverse highlighted by human mouse disorders elicited mutations their genes. These pathologies include neurodegeneration, leukodystrophy, mental retardation, deafness, blindness, myotonia, hyperaldosteronism, renal salt loss, proteinuria, kidney stones, male infertility, osteopetrosis. this review, emphasis is laid cell biological organismal mammalian role disease.

Language: Английский

Citations

394
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

Citations

231
DNA methylation analysis on purified neurons and glia dissects age and Alzheimer’s disease-specific changes in the human cortex DOI Creative Commons
Gilles Gasparoni, Sebastian Bultmann, Pavlo Lutsik

et al.

Epigenetics & Chromatin, Journal Year: 2018, Volume and Issue: 11(1)

Published: July 25, 2018

Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer's disease (AD). However, strong variation cell-type proportions across tissue represents significant source data noise. Here, we report the first EWAS sorted neuronal non-neuronal (mostly glia) nuclei from postmortem tissues.We show that cell sorting strongly enhances robust detection disease-related DNA methylation changes even relatively small cohort. We identify numerous genes with cell-type-specific signatures document differential dynamics associated aging specifically neurons such as CLU, SYNJ2 NCOR2 or glia RAI1,CXXC5 INPP5A. Further, found neuron glia-specific associations AD Braak stage progression at MCF2L, ANK1, MAP2, LRRC8B, STK32C S100B. A comparison our study previous tissue-based validates multiple AD-associated signals additionally specifies their origin to neuron, e.g., HOXA3 (ANK1). In meta-analysis, reveal two novel previously unrecognized key risk APP ADAM17.Our highlight complex interplay between disease, age thus offering new perspectives for validation interpretation large results.

Language: Английский

Citations

209
Glutamate-Releasing SWELL1 Channel in Astrocytes Modulates Synaptic Transmission and Promotes Brain Damage in Stroke DOI Creative Commons
Junhua Yang, Maria del Carmen Vitery, Jianan Chen

et al.

Neuron, Journal Year: 2019, Volume and Issue: 102(4), P. 813 - 827.e6

Published: April 11, 2019

Language: Английский

Citations

205
Structure of a volume-regulated anion channel of the LRRC8 family DOI
Dawid Deneka, Marta Sawicka, Andy K.M. Lam

et al.

Nature, Journal Year: 2018, Volume and Issue: 558(7709), P. 254 - 259

Published: May 14, 2018

Language: Английский

Citations

182
ATP Release Channels DOI Open Access
Akiyuki Taruno

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(3), P. 808 - 808

Published: March 11, 2018

Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms cellular ATP release have demonstrated in many cell types. Although large negatively charged molecules cannot diffuse across lipid bilayer plasma membrane, conductive from cytosol into space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for permeation: anion permeability a ion-conducting pore. Currently, five groups are acknowledged ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated (VRACs, also known volume-sensitive outwardly rectifying (VSOR) channels), maxi-anion (MACs). Recently, major breakthroughs made field by molecular identification CALHM1 action potential-dependent channel taste bud cells, LRRC8s components VRACs, SLCO2A1 core subunit MACs. Here, function roles these summarized, along discussion on future implications understanding

Language: Английский

Citations

175
LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP DOI Creative Commons
Lauren J. Lahey,

Rachel E. Mardjuki,

Xianlan Wen

et al.

Molecular Cell, Journal Year: 2020, Volume and Issue: 80(4), P. 578 - 591.e5

Published: Nov. 1, 2020

Language: Английский

Citations

146
Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke DOI Open Access

Zihuan Shen,

Mi Xiang, Chen Chen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 151, P. 113125 - 113125

Published: May 24, 2022

Glutamate-mediated excitotoxicity is an important mechanism leading to post ischemic stroke damage. After acute stroke, the sudden reduction in cerebral blood flow most initially followed by ion transport protein dysfunction and disruption of homeostasis, which turn leads impaired glutamate release, reuptake, excessive N-methyl-D-aspartate receptor (NMDAR) activation, promoting neuronal death. Despite extensive evidence from preclinical studies suggesting that NMDAR stimulation during a central step post-stroke damage, blockers have failed translate into clinical treatment. Current treatment options for are very limited, there therefore great need develop new targets neuroprotective therapeutic agents extend time window. In this review, we highlight recent findings on reuptake mechanisms, its downstream cellular signaling pathways post-ischemic review pathological changes each link help viable targets. We then also summarize potential drugs approaches these stroke.

Language: Английский

Citations

132
GABA tone regulation and its cognitive functions in the brain DOI
Wuhyun Koh, Hankyul Kwak, Eunji Cheong

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(9), P. 523 - 539

Published: July 26, 2023

Language: Английский

Citations

98
The volume-regulated anion channel LRRC8C suppresses T cell function by regulating cyclic dinucleotide transport and STING–p53 signaling DOI
Axel R. Concepcion, Larry E. Wagner, Jingjie Zhu

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 287 - 302

Published: Feb. 1, 2022

Language: Английский

Citations

81