keyword
MENU ▼
Read by QxMD icon Read
search

Tmem16a

keyword
https://www.readbyqxmd.com/read/27860832/anoctamins-tmem16-proteins-chloride-channels-flirting-with-lipids-and-extracellular-vesicles
#1
Jarred M Whitlock, H Criss Hartzell
Anoctamin/TMEM16 proteins exhibit diverse functions in cells throughout the body and are implicated in several human diseases. Although the founding members ANO1 (TMEM16A) and ANO2 (TMEM16B) are Ca(2+)-activated Cl(-) channels, most ANO paralogs are Ca(2+)-dependent phospholipid scramblases that serve as channels facilitating the movement (scrambling) of phospholipids between leaflets of the membrane bilayer. Phospholipid scrambling significantly alters the physical properties of the membrane and its landscape and has vast downstream signaling consequences...
November 16, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27859335/extracellular-protons-enable-activation-of-the-calcium-dependent-chloride-channel-tmem16a-ano1
#2
Silvia Cruz-Rangel, José J De Jesus-Pérez, Iván A Aréchiga-Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola
TMEM16A (ANO1), the pore forming subunit of a Ca(2+) -dependent Cl(-) channel (CaCC), is activated by direct, voltage-dependent, binding of intracellular Ca(2+) . Endogenous CaCCs are regulated by extracellular protons; however, the molecular basis of such regulation remains unidentified. Here, we evaluated the effects of different extracellular proton concentrations ([H(+) ]o ) on mouse TMEM16A expressed in HEK-293 cells using whole-cell and inside-out patch clamp recordings. We found that increasing the [H(+) ]o from 10(-10) to 10(-5...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27799319/independent-activation-of-distinct-pores-in-dimeric-tmem16a-channels
#3
Grace Jeng, Muskaan Aggarwal, Wei-Ping Yu, Tsung-Yu Chen
The TMEM16 family encompasses Ca(2+)-activated Cl(-) channels (CaCCs) and lipid scramblases. These proteins are formed by two identical subunits, as confirmed by the recently solved crystal structure of a TMEM16 lipid scramblase. However, the high-resolution structure did not provide definitive information regarding the pore architecture of the TMEM16 channels. In this study, we express TMEM16A channels constituting two covalently linked subunits with different Ca(2+) affinities. The dose-response curve of the heterodimer appears to be a weighted sum of two dose-response curves-one corresponding to the high-affinity subunit and the other to the low-affinity subunit...
November 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27799318/independent-activation-of-ion-conduction-pores-in-the-double-barreled-calcium-activated-chloride-channel-tmem16a
#4
Novandy K Lim, Andy K M Lam, Raimund Dutzler
The TMEM16 proteins constitute a family of membrane proteins with unusual functional breadth, including lipid scramblases and Cl(-) channels. Members of both these branches are activated by Ca(2+), acting from the intracellular side, and probably share a common architecture, which was defined in the recent structure of the lipid scramblase nhTMEM16. The structural features of subunits and the arrangement of Ca(2+)-binding sites in nhTMEM16 suggest that the dimeric protein harbors two locations for catalysis that are independent with respect to both activation and lipid conduction...
November 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27799301/anoctamin-6-contributes-to-cl-secretion-in-accessory-cholera-enterotoxin-ace-stimulated-diarrhea-an-essential-role-for-pip2-signaling-in-cholera
#5
Joydeep Aoun, Mikio Hayashi, Irshad Ali Sheikh, Paramita Sarkar, Tultul Saha, Priyanka Ghosh, Rajsekhar Bhowmick, Dipanjan Ghosh, Tanaya Chatterjee, Pinak Chakrabarti, Manoj K Chakrabarti, Kazi Mirajul Hoque
Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea However, the signaling mechanism and specific type of Cl- channel activated by Ace is yet unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane which were inhibited by classical CaCC blockers. Surprisingly, Ace elicited rise of current was neither affected by Ano1 (Tmem16a) specific inhibitor T16A(inh)-AO1(TAO1) nor by CFTR blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27786259/goblet-cell-hyperplasia-requires-high-bicarbonate-transport-to-support-mucin-release
#6
Giulia Gorrieri, Paolo Scudieri, Emanuela Caci, Marco Schiavon, Valeria Tomati, Francesco Sirci, Francesco Napolitano, Diego Carrella, Ambra Gianotti, Ilaria Musante, Maria Favia, Valeria Casavola, Lorenzo Guerra, Federico Rea, Roberto Ravazzolo, Diego Di Bernardo, Luis J V Galietta
Goblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 and IL-13. In human bronchial epithelial cells, we find that IL-4 induces the expression of many genes coding for ion channels and transporters, including TMEM16A, SLC26A4, SLC12A2, and ATP12A. At the functional level, we find that IL-4 enhances calcium- and cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration and alkaline pH in the fluid covering the apical surface of epithelia...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721237/store-operated-ca2-entry-regulates-ca2-activated-chloride-channels-and-eccrine-sweat-gland-function
#7
Axel R Concepcion, Martin Vaeth, Larry E Wagner, Miriam Eckstein, Lee Hecht, Jun Yang, David Crottes, Maximilian Seidl, Hyosup P Shin, Carl Weidinger, Scott Cameron, Stuart E Turvey, Thomas Issekutz, Isabelle Meyts, Rodrigo S Lacruz, Mario Cuk, David I Yule, Stefan Feske
Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27682822/new-insights-on-the-regulation-of-ca-2-activated-chloride-channel-tmem16a
#8
Ke Ma, Hui Wang, Jiankun Yu, Minjie Wei, Qinghuan Xiao
TMEM16A, also known as anoctamin 1, is a recently identified Ca(2+) -activated chloride channel and the first member of a 10-member TMEM16 family. TMEM16A dysfunction is implicated in many diseases such as cancer, hypertension, and cystic fibrosis. TMEM16A channels are well known to be dually regulated by voltage and Ca(2+) . In addition, recent studies have revealed that TMEM16A channels are regulated by many molecules such as calmodulin, protons, cholesterol, and phosphoinositides, and a diverse range of stimuli such as thermal and mechanical stimuli...
September 28, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27621452/correction-for-tien-et-al-identification-of-a-dimerization-domain-in-the-tmem16a-calcium-activated-chloride-channel-cacc
#9
(no author information available yet)
No abstract text is available yet for this article.
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27601995/shikonin-inhibits-intestinal-calcium-activated-chloride-channels-and-prevents-rotaviral-diarrhea
#10
Yu Jiang, Bo Yu, Hong Yang, Tonghui Ma
Secretory diarrhea remains a global health burden and causes major mortality in children. There have been some focuses on antidiarrheal therapies that may reduce fluid losses and intestinal motility in diarrheal diseases. In the present study, we identified shikonin as an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. The IC50 value of shikonin was 6.5 μM. Short-circuit current measurements demonstrated that shikonin inhibited Eact-induced Cl(-) current in a dose-dependent manner, with IC50 value of 1...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27588910/interleukin-13-stimulates-muc5ac-expression-via-a-stat6-tmem16a-erk1-2-pathway-in-human-airway-epithelial-cells
#11
Yanling Qin, Youfan Jiang, Awais Shafiq Sheikh, Shanshan Shen, Jing Liu, Depeng Jiang
Transmembrane protein 16A (TMEM16A), a channel underlying the calcium-activated chloride channel (CaCC) currents, has been shown to be a key regulator of mucus overproduction in airway epithelial cells. However, the precise molecular mechanism involved in the TMEM16A-mediated mucus secretion remains unclear. In the present study, we inquired into a novel signaling mechanism for TMEM16A driving mucin 5AC (MUC5AC) production in human airway epithelial cells. Following treatment for 24-48h with type 13 interleukin (IL-13), an upregulation of TMEM16A expression in both mRNA and protein levels was observed in human bronchial epithelial cell line (HBE16), while signal transducer and activator of transcription 6 (STAT6) inhibition could decrease this elevated expression, suggesting that the regulation of TMEM16A expression by IL-13 was via a STAT6-based transcriptional mechanism...
August 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27558156/ca2-activated-cl-channel-currents-in-mammary-secretory-cells-from-lactating-mouse
#12
Akihiro Kamikawa, Osamu Ichii, Junpei Sakazaki, Toru Ishikawa
The Cl(-) secretion via Ca(2+)-activated Cl(-) channel (CaCC) is critical for fluid secretion in exocrine glands like the salivary gland. Also in the mammary gland, it has been hypothesized that CaCC plays an important role in the secretion of Cl(-) and aqueous phase of milk. However, there has been no evidence for the functional expression of CaCC in native mammary secretory (MS) cells of lactating animals. We therefore assessed the membrane current in the MS cells that were freshly isolated from lactating mice using the whole-cell patch-clamp techniques...
August 24, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27514381/relationship-between-tmem16a-anoctamin-1-and-lrrc8a
#13
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/27510033/hco3-transport-through-anoctamin-transmembrane-protein-ano1-tmem16a-in-pancreatic-acinar-cells-regulates-luminal-ph
#14
Yanfeng Han, Annette M Shewan, Peter Thorn
The identification of ANO1/TMEM16A as the likely calcium-dependent chloride channel of exocrine glands has led to a more detailed understanding of its biophysical properties. This includes a calcium-dependent change in channel selectivity and evidence that HCO3 (-) permeability can be significant. Here we use freshly isolated pancreatic acini that preserve the luminal structure to measure intraluminal pH and test the idea that ANO1/TMEM16A contributes to luminal pH balance. Our data show that, under physiologically relevant stimulation with 10 pm cholesystokinin, the luminal acid load that results from the exocytic fusion of zymogen granules is significantly blunted by HCO3 (-) buffer in comparison with HEPES, and that this is blocked by the specific TMEM16A inhibitor T16inh-A01...
September 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27219012/ani9-a-novel-potent-small-molecule-ano1-inhibitor-with-negligible-effect-on-ano2
#15
Yohan Seo, Ho K Lee, Jinhong Park, Dong-Kyu Jeon, Sungwoo Jo, Minjae Jo, Wan Namkung
Anoctamin1 (ANO1)/transmembrane protein 16A (TMEM16A), a calcium-activated chloride channel (CaCC), is involved in many physiological functions such as fluid secretion, smooth muscle contraction, nociception and cancer progression. To date, only a few ANO1 inhibitors have been described, and these have low potency and selectivity for ANO1. Here, we performed a high-throughput screening to identify highly potent and selective small molecule inhibitors of ANO1. Three novel ANO1 inhibitors were discovered from screening of 54,400 synthetic small molecules, and they were found to fully block ANO1 channel activity with an IC50 < 3 μM...
2016: PloS One
https://www.readbyqxmd.com/read/27189885/sarcolemmal-ca-2-entry-through-l-type-ca-2-channels-controls-the-profile-of-ca-2-activated-cl-current-in-canine-ventricular-myocytes
#16
Balázs Horváth, Krisztina Váczi, Bence Hegyi, Mónika Gönczi, Beatrix Dienes, Kornél Kistamás, Tamás Bányász, János Magyar, István Baczkó, András Varró, György Seprényi, László Csernoch, Péter P Nánási, Norbert Szentandrássy
Ca(2+)-activated Cl(-) current (ICl(Ca)) mediated by TMEM16A and/or Bestrophin-3 may contribute to cardiac arrhythmias. The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood. We aimed to study the profile of ICl(Ca) systematically under physiological conditions (normal Ca(2+) cycling and AP voltage-clamp) as well as in conditions designed to change [Ca(2+)]i. The expression of TMEM16A and/or Bestrophin-3 in canine and human left ventricular myocytes was examined...
August 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27168798/nsaids-modulate-gaba-activated-currents-via-ca-2-activated-cl-channels-in-rat-dorsal-root-ganglion-neurons
#17
Lei Zhao, L I Li, Ke-Tao Ma, Yang Wang, Jing Li, Wen-Yan Shi, H E Zhu, Zhong-Shuang Zhang, Jun-Qiang Si
The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to modulate γ-aminobutyrate (GABA)-activated currents via Ca(2+)-activated Cl(-) channels in rat dorsal root ganglion neurons (DRG), was examined in the present study. During the preparation of DRG neurons harvested from Sprague-Dawley rats, the whole-cell recording technique was used to record the effect of NSAIDs on GABA-activated inward currents, and the expression levels of the TMEM16A and TMEM16B subunits were revealed. In the event that DRG neurons were pre-incubated for 20 sec with niflumic acid (NFA) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) prior to the administration of GABA, the GABA-induced inward currents were diminished markedly in the majority of neurons examined (96...
May 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27147559/local-coupling-of-trpc6-to-ano1-tmem16a-channels-in-smooth-muscle-cells-amplifies-vasoconstriction-in-cerebral-arteries
#18
Qian Wang, M Dennis Leo, Damodaran Narayanan, Korah P Kuruvilla, Jonathan H Jaggar
Anoctamin-1 [ANO1, also known as transmembrane protein 16A (TMEM16A)] is a Ca(2+)-activated Cl(-) channel expressed in arterial myocytes that regulates membrane potential and contractility. Signaling mechanisms that control ANO1 activity in arterial myocytes are poorly understood. In cerebral artery myocytes, ANO1 channels are activated by local Ca(2+) signals generated by plasma membrane nonselective cation channels, but the molecular identity of these proteins is unclear. Arterial myocytes express several different nonselective cation channels, including multiple members of the transient receptor potential receptor (TRP) family...
June 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27138167/revealing-the-activation-pathway-for-tmem16a-chloride-channels-from-macroscopic-currents-and-kinetic-models
#19
Juan A Contreras-Vite, Silvia Cruz-Rangel, José J De Jesús-Pérez, Iván A Aréchiga Figueroa, Aldo A Rodríguez-Menchaca, Patricia Pérez-Cornejo, H Criss Hartzell, Jorge Arreola
TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca(2+)]i), membrane depolarization, extracellular Cl(-) or permeant anions and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations...
July 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27101932/the-molecular-basis-of-the-genesis-of-basal-tone-in-internal-anal-sphincter
#20
Cheng-Hai Zhang, Pei Wang, Dong-Hai Liu, Cai-Ping Chen, Wei Zhao, Xin Chen, Chen Chen, Wei-Qi He, Yan-Ning Qiao, Tao Tao, Jie Sun, Ya-Jing Peng, Ping Lu, Kaizhi Zheng, Siobhan M Craige, Lawrence M Lifshitz, John F Keaney, Kevin E Fogarty, Ronghua ZhuGe, Min-Sheng Zhu
Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca(2+) channels (VDCCs) or TMEM16A Ca(2+)-activated Cl(-) channels significantly changes global cytosolic Ca(2+) concentration ([Ca(2+)]i) and the tone...
April 22, 2016: Nature Communications
keyword
keyword
25425
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"