The Water Transport System in Astrocytes–Aquaporins DOI Creative Commons
Zuoyi Zhou, Jiangshan Zhan,

Qingyun Cai

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2564 - 2564

Published: Aug. 18, 2022

Astrocytes have distinctive morphological and functional characteristics, are found throughout the central nervous system. now known to be far more than just housekeeping cells in brain. Their functions include contributing formation of blood–brain barrier, physically metabolically supporting communicating with neurons, regulating synapses, maintaining water homeostasis microenvironment Aquaporins (AQPs) transmembrane proteins responsible for fast movement across cell membranes. Various subtypes AQPs (AQP1, AQP3, AQP4, AQP5, AQP8 AQP9) been reported expressed astrocytes, expressions subcellular localizations astrocytes highly correlated both their physiological pathophysiological functions. This review describes summarizes recent advances our understanding regard controlling Findings regarding features different AQP subtypes, such as expression, localization, functions, roles presented, brain edema glioma serving two representative AQP-associated pathological conditions. The aim is provide a better insight into elaborate “water distribution” system cells, exemplified by under normal

Language: Английский

Biological synthesis of metallic nanoparticles (MNPs) by plants and microbes: their cellular uptake, biocompatibility, and biomedical applications DOI
Fiaz Ahmad,

Noreen Ashraf,

Tayyba Ashraf

et al.

Applied Microbiology and Biotechnology, Journal Year: 2019, Volume and Issue: 103(7), P. 2913 - 2935

Published: Feb. 18, 2019

Language: Английский

Citations

125
Cryo-EM structures of the human volume-regulated anion channel LRRC8 DOI
Go Kasuya, Takanori Nakane, Takeshi Yokoyama

et al.

Nature Structural & Molecular Biology, Journal Year: 2018, Volume and Issue: 25(9), P. 797 - 804

Published: Aug. 17, 2018

Language: Английский

Citations

115
A look at the smelly side of physiology: transport of short chain fatty acids DOI
Friederike Stumpff

Pflügers Archiv - European Journal of Physiology, Journal Year: 2018, Volume and Issue: 470(4), P. 571 - 598

Published: Jan. 6, 2018

Language: Английский

Citations

114
Biomimetic membranes: A critical review of recent progress DOI
Adewale Giwa, Shadi W. Hasan, Abu Yousuf

et al.

Desalination, Journal Year: 2017, Volume and Issue: 420, P. 403 - 424

Published: July 1, 2017

Language: Английский

Citations

108
Molecular Biology and Physiology of Volume-Regulated Anion Channel (VRAC) DOI Creative Commons
James Osei-Owusu, Junhua Yang, Maria del Carmen Vitery

et al.

Current topics in membranes, Journal Year: 2018, Volume and Issue: unknown, P. 177 - 203

Published: Jan. 1, 2018

Language: Английский

Citations

106
Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs DOI Creative Commons
David M. Kern, SeCheol Oh, Richard K. Hite

et al.

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Feb. 18, 2019

Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A homo- or hetero-hexameric assemblies. Here, we present single-particle cryo-electron microscopy structures of Mus musculus complex with the inhibitor DCPIB reconstituted lipid nanodiscs. plugs channel like a cork bottle - binding extracellular selectivity filter sterically occluding ion conduction. Constricted expanded reveal coupled dilation cytoplasmic LRRs pore, suggesting mechanism for gating internal stimuli. Conformational symmetry differences between determined detergent micelles bilayers related to reorganization intersubunit sites demonstrate critical role membrane determining structure. results provide insight into LRRC8 inhibition lipids structure an ionic-strength sensing channel.

Language: Английский

Citations

98
Intracellular Chloride Channels: Novel Biomarkers in Diseases DOI Creative Commons
Shubha Gururaja Rao,

Neel Patel,

Harpreet Singh

et al.

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: Feb. 14, 2020

Ion channels are integral membrane proteins present on the plasma as well intracellular membranes. It had been long thought that transmembrane ion fluxes depend conduction pathways located within a specific group of given lipid bilayer was characterized impermeable to water-soluble ions. Only in 1980s, convergence state-of-the-art biophysical and molecular biological techniques allowed in-depth characterization identification responsible for fluxes. In human genome, there more than 400 known genes encoding channels. On changing their conformation from closed open states, they allow ions flow through them albeit tightly regulating ionic flux. regulate several cellular, organellar physiological processes, any mutation or disruption function can result common (tumors) rare pathological disorders. widely acknowledged role various processes but recent years, studies have pointed out importance Intracellular not well-understood context conditions such oncochannelopathies therapeutic targets cancer. A novel class channels, Chloride Channels (CLICs), mainly documented cardiovascular neurophysiology, tumor biology. They recently shown be localized mitochondria. fact, CLIC5 is first mitochondrial chloride channel identified up level inner membrane, CLIC4 predominantly outer this review, we focused unique pathologies include cardiovascular, cancer neurodegenerative diseases.

Language: Английский

Citations

98
Molecular composition and heterogeneity of the LRRC8‐containing swelling‐activated osmolyte channels in primary rat astrocytes DOI Open Access
Alexandra L. Schober,

Corinne S. Wilson,

Alexander A. Mongin

et al.

The Journal of Physiology, Journal Year: 2017, Volume and Issue: 595(22), P. 6939 - 6951

Published: Aug. 22, 2017

Key points The volume‐regulated anion channel (VRAC) is a swelling‐activated chloride that permeable to inorganic anions and variety of small organic molecules. VRAC formed via heteromerization LRRC8 proteins, among which LRRC8A essential, while LRRC8B/C/D/E serve as exchangeable complementary partners. We used an RNAi approach radiotracer assays explore isoforms contribute release diverse osmolytes in rat astrocytes. Efflux uncharged ( my o‐inositol taurine) was suppressed by deletion or LRRC8D, but not LRRC8C+LRRC8E. Conversely, charged d ‐aspartate) strongly reduced LRRC8C+LRRC8E, largely unaffected downregulation LRRC8D. Our findings point the existence multiple heteromeric VRACs same cell type: LRRC8A/D‐containing heteromers appear dominate osmolytes, LRRC8A/C/E, with additional contribution creates conduit for movement Abstract ubiquitously expressed vertebrate Cl − /anion composed proteins belonging family activated swelling. In brain, contributes physiological pathological molecules, including amino acid neurotransmitters glutamate, aspartate taurine. present work, we explored role all five members from primary Expression modified using approach, fluxes were quantified cells challenged hypoosmotic medium (30% reduction osmolarity). Consistent our prior knockdown potently equally radiolabelled ‐[ 14 C]aspartate [ 3 H]taurine. Among other subunits, LRRC8D inhibited H]taurine myo H]inositol, without major impact on simultaneously measured efflux C]aspartate. contrast, preferentially sensitive Finally, siRNA LRRC8C+LRRC8D osmolytes. Overall, suggest at least two distinct astroglial cells. permeability pathway appears alternative (or channels) LRRC8A/C/D/E responsible loss

Language: Английский

Citations

95
Cells recognize osmotic stress through liquid–liquid phase separation lubricated with poly(ADP-ribose) DOI Creative Commons
Kengo Watanabe, Kazuhiro Morishita, Xiangyu Zhou

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 1, 2021

Abstract Cells are under threat of osmotic perturbation; cell volume maintenance is critical in cerebral edema, inflammation and aging, which prominent changes intracellular or extracellular osmolality emerge. After stress-enforced swelling shrinkage, the cells regulate to recover their volume. However, mechanisms recognizing stress remain obscured. We previously clarified that apoptosis signal-regulating kinase 3 (ASK3) bidirectionally responds regulates recovery. Here, we show macromolecular crowding induces liquid-demixing condensates ASK3 hyperosmotic stress, transduce osmosensing signal into inactivation. A genome-wide small interfering RNA (siRNA) screen identifies an inactivation regulator, nicotinamide phosphoribosyltransferase (NAMPT), related poly(ADP-ribose) signaling. Furthermore, clarify keeps liquid phase enables become inactivated stress. Our findings demonstrate rationally incorporate physicochemical separation systems.

Language: Английский

Citations

89
A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel DOI Creative Commons

Kevin Strange,

Toshiki Yamada, Jerod S. Denton

et al.

The Journal of General Physiology, Journal Year: 2019, Volume and Issue: 151(2), P. 100 - 117

Published: Jan. 16, 2019

The swelling-activated anion channel VRAC has fascinated and frustrated physiologists since it was first described in 1988. Multiple laboratories have defined VRAC's biophysical properties shown that plays a central role cell volume regulation possibly other fundamental physiological processes. However, confusion intense controversy surrounding the channel's molecular identity greatly hindered progress field for >15 yr. A major breakthrough came 2014 with demonstration is heteromeric encoded by five members of Lrrc8 gene family, Lrrc8A-E. mere 4 yr later, four cryo-EM structures LRRC8A homomeric channels. As melee structure/function physiology studies begins, critical this work be framed clear understanding biophysics, regulation, cellular as well field's past controversies. That essential design interpretation studies, physiology, aimed at addressing vexing problem how detects changes. In review we discuss key aspects function integrate these into our emerging LRRC8 protein structure/function.

Language: Английский

Citations

86