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https://www.readbyqxmd.com/read/28298618/new-insights-into-vrac-composition-and-substrates
#1
(no author information available yet)
No abstract text is available yet for this article.
March 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28289711/the-volume-regulated-anion-channel-lrrc8-in-nodose-neurons-is-sensitive-to-acidic-ph
#2
Runping Wang, Yongjun Lu, Susheel Gunasekar, Yanhui Zhang, Christopher J Benson, Mark W Chapleau, Rajan Sah, François M Abboud
The leucine rich repeat containing protein 8A (LRRC8A), or SWELL1, is an essential component of the volume-regulated anion channel (VRAC) that is activated by cell swelling and ionic strength. We report here for the first time to our knowledge its expression in a primary cell culture of nodose ganglia neurons and its localization in the soma, neurites, and neuronal membrane. We show that this neuronal VRAC/SWELL1 senses low external pH (pHo) in addition to hypoosmolarity. A robust sustained chloride current is seen in 77% of isolated nodose neurons following brief exposures to extracellular acid pH...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193731/selective-transport-of-neurotransmitters-and-modulators-by-distinct-volume-regulated-lrrc8-anion-channels
#3
Darius Lutter, Florian Ullrich, Jennifer C Lueck, Stefan Kempa, Thomas J Jentsch
In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine...
February 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28192143/lrrc8a-dependent-volume-regulated-anion-channel-activity-is-dispensable-for-t-cell-development-and-function
#4
Craig D Platt, Janet Chou, Patrick Houlihan, Yousef R Badran, Lalit Kumar, Wayne Bainter, P Luigi Poliani, Carlos J Perez, Sharon Y R Dent, David E Clapham, Fernando Benavides, Raif S Geha
BACKGROUND: Leucine-rich repeat containing 8A (LRRC8A) is a ubiquitously expressed transmembrane protein with 17 LRRs at its C-terminal end, and is an essential component of the volume regulated anion channel (VRAC) which controls cellular volume. A heterozygous mutation in LRRC8A that truncates the two terminal LRRs was reported in a patient with agammaglobulinemia and absent B cells, and was demonstrated to exert a dominant negative effect on T and B cell development in mice. Lrrc8a(-/-) mice have severely defective T cell development and function...
February 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28130109/hypotonicity-activates-a-voltage-dependent-membrane-conductance-in-n2a-neuroblastoma-cells
#5
Akiyuki Taruno, Yoshinori Marunaka
To maintain cellular and bodily homeostasis, cells respond to extracellular stimuli including osmotic stress by activating various ion channels, which have been implicated in many physiological and pathophysiological conditions. However, cellular osmosensory mechanisms remain elusive. Here, we report a novel voltage-dependent current in N2a cells activated by exposure to hypotonic stress. After a hypotonic challenge, N2a cells sequentially develop two distinct currents. The volume-regulated anion channel (VRAC) current emerges first and, after a delay, activation of a previously uncharacterized strongly outwardly rectifying current follows...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28121479/cisplatin-activates-volume-sensitive-lrrc8-channel-mediated-currents-in-xenopus-oocytes
#6
Antonella Gradogna, Héctor Gaitán-Peñas, Anna Boccaccio, Raúl Estévez, Michael Pusch
LRRC8 proteins have been shown to underlie the ubiquitous volume regulated anion channel (VRAC). VRAC channels are composed of the LRRC8A subunit and at least one among the LRRC8B-E subunits. In addition to their role in volume regulation, LRRC8 proteins have been implicated in the uptake of chemotherapeutic agents. We had found that LRRC8 channels can be conveniently expressed in Xenopus oocytes, a system without endogenous VRAC activity. The fusion with fluorescent proteins yielded constitutive activity for A/C, A/D and A/E heteromers...
January 25, 2017: Channels
https://www.readbyqxmd.com/read/27875957/editorial
#7
Subhash C Basak, Marjan Vrac Ko, Frank A Witzmann
No abstract text is available yet for this article.
2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27796579/calcium-is-not-required-for-triggering-volume-restoration-in-hypotonically-challenged-a549-epithelial-cells
#8
Olga Ponomarchuk, Francis Boudreault, Sergei N Orlov, Ryszard Grygorczyk
Maintenance of cell volume is a fundamental housekeeping function in eukaryotic cells. Acute cell swelling activates a regulatory volume decrease (RVD) process with poorly defined volume sensing and intermediate signaling mechanisms. Here, we analyzed the putative role of Ca(2+) signaling in RVD in single substrate-adherent human lung epithelial A549 cells. Acute cell swelling was induced by perfusion of the flow-through imaging chamber with 50 % hypotonic solution at a defined fluid turnover rate. Changes in cytosolic Ca(2+) concentration ([Ca(2+)]i) and cell volume were monitored simultaneously with ratiometric Fura-2 fluorescence and 3D reconstruction of stereoscopic single-cell images, respectively...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27764579/specific-and-essential-but-not-sufficient-roles-of-lrrc8a-in-the-activity-of-volume-sensitive-outwardly-rectifying-anion-channel-vsor
#9
Toshiaki Okada, Md Rafiqul Islam, Nargiza A Tsiferova, Yasunobu Okada, Ravshan Z Sabirov
The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of 4 other types of anion channel activated by acid, Ca(2+), patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells...
October 20, 2016: Channels
https://www.readbyqxmd.com/read/27705766/investigation-of-lrrc8-mediated-volume-regulated-anion-currents-in-xenopus-oocytes
#10
Héctor Gaitán-Peñas, Antonella Gradogna, Lara Laparra-Cuervo, Carles Solsona, Victor Fernández-Dueñas, Alejandro Barrallo-Gimeno, Francisco Ciruela, Melike Lakadamyali, Michael Pusch, Raúl Estévez
Volume-regulated anion channels (VRACs) play an important role in controlling cell volume by opening upon cell swelling. Recent work has shown that heteromers of LRRC8A with other LRRC8 members (B, C, D, and E) form the VRAC. Here, we used Xenopus oocytes as a simple system to study LRRC8 proteins. We discovered that adding fluorescent proteins to the C-terminus resulted in constitutive anion channel activity. Using these constructs, we reproduced previous findings indicating that LRRC8 heteromers mediate anion and osmolyte flux with subunit-dependent kinetics and selectivity...
October 4, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27688432/leucine-rich-repeat-containing-protein-lrrc8a-is-essential-for-swelling-activated-cl-currents-and-embryonic-development-in-zebrafish
#11
Toshiki Yamada, Robert Wondergem, Rebecca Morrison, Viravuth P Yin, Kevin Strange
A volume-regulated anion channel (VRAC) has been electrophysiologically characterized in innumerable mammalian cell types. VRAC is activated by cell swelling and mediates the volume regulatory efflux of Cl(-) and small organic solutes from cells. Two groups recently identified the mammalian leucine-rich repeat containing protein LRRC8A as an essential VRAC component. LRRC8A must be coexpressed with at least one of the other four members of this gene family, LRRC8B-E, to reconstitute VRAC activity in LRRC8(-/-) cells...
October 2016: Physiological Reports
https://www.readbyqxmd.com/read/27514381/relationship-between-tmem16a-anoctamin-1-and-lrrc8a
#12
Roberta Benedetto, Lalida Sirianant, Ines Pankonien, Podchanart Wanitchakool, Jiraporn Ousingsawat, Ines Cabrita, Rainer Schreiber, Margarida Amaral, Karl Kunzelmann
TMEM16A/anoctamin 1/ANO1 and VRAC/LRRC8 are independent chloride channels activated either by increase in intracellular Ca(2+) or cell swelling, respectively. In previous studies, we observed overlapping properties for both types of channels. (i) TMEM16A/ANO1 and LRRC8 are inhibited by identical compounds, (ii) the volume-regulated anion channel VRAC requires compartmentalized Ca(2+) increase to be fully activated, (iii) anoctamins are activated by cell swelling, (iv) both channels have a role for apoptotic cell death, (v) both channels are possibly located in lipid rafts/caveolae like structures, and (vi) VRAC and anoctamin 1 currents are not additive when each are fully activated...
October 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27358231/channels-and-volume-changes-in-the-life-and-death-of-the-cell
#13
Herminia Pasantes-Morales
Volume changes deviating from original cell volume represent a major challenge for cellular homeostasis. Cell volume may be altered either by variations in the external osmolarity or by disturbances in the transmembrane ion gradients that generate an osmotic imbalance. Cells respond to anisotonicity-induced volume changes by active regulatory mechanisms that modify the intracellular/extracellular concentrations of K(+), Cl(-), Na(+), and organic osmolytes in the direction necessary to reestablish the osmotic equilibrium...
September 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27325695/inactivation-and-anion-selectivity-of-volume-regulated-anion-channels-vracs-depend-on-c-terminal-residues-of-the-first-extracellular-loop
#14
Florian Ullrich, S Momsen Reincke, Felizia K Voss, Tobias Stauber, Thomas J Jentsch
Canonical volume-regulated anion channels (VRACs) are crucial for cell volume regulation and have many other important roles, including tumor drug resistance and release of neurotransmitters. Although VRAC-mediated swelling-activated chloride currents (ICl,vol) have been studied for decades, exploration of the structure-function relationship of VRAC has become possible only after the recent discovery that VRACs are formed by differently composed heteromers of LRRC8 proteins. Inactivation of ICl,vol at positive potentials, a typical hallmark of VRACs, strongly varies between native cell types...
August 12, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27122993/fluoride-induces-a-volume-reduction-in-ca1-hippocampal-slices-via-map-kinase-pathway-through-volume-regulated-anion-channels
#15
Jaekwang Lee, Young-Eun Han, Oleg Favorov, Mark Tommerdahl, Barry Whitsel, C Justin Lee
Regulation of cell volume is an important aspect of cellular homeostasis during neural activity. This volume regulation is thought to be mediated by activation of specific transporters, aquaporin, and volume regulated anion channels (VRAC). In cultured astrocytes, it was reported that swelling-induced mitogen-activated protein (MAP) kinase activation is required to open VRAC, which are thought to be important in regulatory volume decrease and in the response of CNS to trauma and excitotoxicity. It has been also described that sodium fluoride (NaF), a recognized G-protein activator and protein phosphatase inhibitor, leads to a significant MAP kinase activation in endothelial cells...
April 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27112899/dual-role-of-lrrc8a-containing-transporters-on-cisplatin-resistance-in-human-ovarian-cancer-cells
#16
Belinda Halling Sørensen, Celina Støving Dam, Stefan Stürup, Ian Henry Lambert
Acquired resistance to chemotherapeutic drugs in cancer cells can reflect an ability to limit cellular drug availability, to repair drug induced DNA damage, and to limit initiation/progression of cell death (apoptosis). The leucine-rich-repeat-containing 8A (LRRC8A) protein is an essential component of volume sensitive channels for organic osmolytes (VSOAC) and volume regulated anion channels (VRAC), which are activated during the apoptotic process. Here we illustrate that cisplatin resistance in human ovarian cancer cells (A2780) correlates with a reduced expression of LRRC8A and copper transporter receptor 1 (CTR1), as well as a concomitant increased expression of copper-transporting P-type ATPases (ATP7A/ATP7B)...
July 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27033257/vracs-and-other-ion-channels-and-transporters-in-the-regulation-of-cell-volume-and-beyond
#17
REVIEW
Thomas J Jentsch
Cells need to regulate their volume to counteract osmotic swelling or shrinkage, as well as during cell division, growth, migration and cell death. Mammalian cells adjust their volume by transporting potassium, sodium, chloride and small organic osmolytes using plasma membrane channels and transporters. This generates osmotic gradients, which drive water in and out of cells. Key players in this process are volume-regulated anion channels (VRACs), the composition of which has recently been identified and shown to encompass LRRC8 heteromers...
May 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/26873248/non-essential-contribution-of-lrrc8a-to-volume-regulation
#18
Lalida Sirianant, Podchanart Wanitchakool, Jiraporn Ousingsawat, Roberta Benedetto, Anna Zormpa, Ines Cabrita, Rainer Schreiber, Karl Kunzelmann
Volume regulation is an essential property of any living cell and needs to be tightly controlled. While different types of K(+) channels have been found to participate in the regulation of cell volume, the newly identified volume-regulated anion channel (VRAC) LRRC8 has been claimed to be essential for volume regulation. In unbiased genome-wide small interfering RNA (siRNA) screens, two independent studies identified LRRC8A/Swell1 as an essential component of VRAC, thus being indispensable for cellular volume regulation...
2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/26824658/lrrc8-proteins-form-volume-regulated-anion-channels-that-sense-ionic-strength
#19
Ruhma Syeda, Zhaozhu Qiu, Adrienne E Dubin, Swetha E Murthy, Maria N Florendo, Daniel E Mason, Jayanti Mathur, Stuart M Cahalan, Eric C Peters, Mauricio Montal, Ardem Patapoutian
The volume-regulated anion channel (VRAC) is activated when a cell swells, and it plays a central role in maintaining cell volume in response to osmotic challenges. SWELL1 (LRRC8A) was recently identified as an essential component of VRAC. However, the identity of the pore-forming subunits of VRAC and how the channel is gated by cell swelling are unknown. Here, we show that SWELL1 and up to four other LRRC8 subunits assemble into heterogeneous complexes of ∼800 kDa. When reconstituted into bilayers, LRRC8 complexes are sufficient to form anion channels activated by osmolality gradients...
January 28, 2016: Cell
https://www.readbyqxmd.com/read/26739710/biophysics-and-physiology-of-the-volume-regulated-anion-channel-vrac-volume-sensitive-outwardly-rectifying-anion-channel-vsor
#20
REVIEW
Stine F Pedersen, Yasunobu Okada, Bernd Nilius
The volume-regulated anion channel (VRAC), also known as the volume-sensitive outwardly rectifying (VSOR) anion channel or the volume-sensitive organic osmolyte/anion channel (VSOAC), is essential for cell volume regulation after swelling in most vertebrate cell types studied to date. In addition to its role in cell volume homeostasis, VRAC has been implicated in numerous other physiological and pathophysiological processes, including cancer, ischemic brain edema, cell motility, proliferation, angiogenesis, programmed cell death, and excitotoxic glutamate release...
March 2016: Pflügers Archiv: European Journal of Physiology
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