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https://www.readbyqxmd.com/read/28099839/trpc5-mediates-acute-leptin-and-serotonin-effects-via-pomc-neurons
#1
Yong Gao, Ting Yao, Zhuo Deng, Jong-Woo Sohn, Jia Sun, Yiru Huang, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hong Chen, Hongbo Guo, Jianqun Yan, Kathryn A Cunningham, Yongsheng Chang, Tiemin Liu, Kevin W Williams
The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28074011/new-connections-nherf-gates-activity
#2
Nancy R Gough
The NHERF molecular adaptors serve as gates for TRPC4 and TRPC5 regulation by diacylglycerol and recognition of CFTR by the quality control checkpoint.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28066924/side-chain-flexibility-and-coupling-between-the-s4-s5-linker-and-the-trp-domain-in-thermo-sensitive-trp-channels-insights-from-protein-modeling
#3
Sergio Romero-Romero, Froylan Gómez-Lagunas, Daniel Balleza
The transient receptor potential (TRP) superfamily is subdivided into several subfamilies on the basis of sequence similarity, which is highly heterogeneous but shows a molecular architecture that resembles the one present in members of the Kv channel superfamily. Because of this diversity, they produce a large variety of channels with different gating and permeability properties. Elucidation of these particular features necessarily requires comparative studies based on structural and functional data. The present study aims to compilate, analyze, and determine, in a coherent way, the relationship between intrinsic side-chain flexibility and the allosteric coupling in members of the TRPV, TRPM, and TRPC families...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28032400/increasing-circulating-exosomes-carrying-trpc5-predicts-chemoresistance-in-metastatic-breast-cancer-patients
#4
Teng Wang, Kuan Ning, Ting-Xun Lu, Xu Sun, Linfang Jin, Xiaowei Qi, Jian Jin, Dong Hua
Chemoresistance, the major obstacle in breast cancer chemotherapy, results in unnecessary chemotherapy and wasting of medical resources. Up to now, no feasible method is available to predict chemoresistance before chemotherapy. In our previously study, elevated expression of transient receptor potential channel TRPC5 was found as an essential element for chemoresistance in breast cancer cells, and could be transferred to chemosensitive breast cancer cells through releasing extracellular vesicles (EVs)-containing TRPC5 from chemoresistant cells, resulting in acquired chemoresistance...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28000878/elevated-expression-of-trpc5-and-glut1-is-associated-with-chemoresistance-in-colorectal-cancer
#5
Teng Wang, Kuan Ning, Ting-Xun Lu, Dong Hua
Reprogramming of energy metabolism (aerobic glycolysis) is thought to play an essential role in cancer. Compared to oxidative phosphorylation, aerobic glycolysis consumes more glucose through the upregulation of glucose transporters, notably glucose transporter 1 (GLUT1). Elevated glycolysis occurs in chemoresistant cancer cells, but the detailed mechanism is not well understood. The upregulation of the Ca2+-permeable transient receptor potential channel 5 (TrpC5) activates the Wnt/β-catenin signaling pathway in 5-fluorouracil (5-Fu)-resistant human colorectal cancer (CRC) HCT-8 (HCT-8/5-Fu) cells...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27994151/dynamic-nherf-interaction-with-trpc4-5-proteins-is-required-for-channel-gating-by-diacylglycerol
#6
Ursula Storch, Anna-Lena Forst, Franziska Pardatscher, Serap Erdogmus, Maximilian Philipp, Manuel Gregoritza, Michael Mederos Y Schnitzler, Thomas Gudermann
The activation mechanism of the classical transient receptor potential channels TRPC4 and -5 via the Gq/11 protein-phospholipase C (PLC) signaling pathway has remained elusive so far. In contrast to all other TRPC channels, the PLC product diacylglycerol (DAG) is not sufficient for channel activation, whereas TRPC4/5 channel activity is potentiated by phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. As a characteristic structural feature, TRPC4/5 channels contain a C-terminal PDZ-binding motif allowing for binding of the scaffolding proteins Na(+)/H(+) exchanger regulatory factor (NHERF) 1 and 2...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27920205/molecular-determinants-of-the-sensitivity-to-gq-11-phospholipase-c-dependent-gating-gd3-potentiation-and-ca2-permeability-in-the-transient-receptor-potential-canonical-type-5-trpc5-channel
#7
Xingjuan Chen, Wennan Li, Ashley M Riley, Mario Soliman, Saikat Chakraborty, Christopher W Stamatkin, Alexander G Obukhov
Transient Receptor Potential Canonical type 5 (TRPC5) is a Ca(2+) permeable cation channel that is highly expressed in the brain and is implicated in motor coordination, innate fear behavior, and seizure-genesis. The channel is activated by a signal downstream of the G-protein-coupled receptor (GPCR)-Gq/11-phospholipase C (PLC) pathway. In this study, we aimed to identify the molecular mechanisms involved in regulating TRPC5 activity. We report that R593, a residue located in the E4 loop near the TRPC5's extracellular Gd(3+)-binding site, is critical for conferring the sensitivity to GPCR-Gq/11-PLC-dependent gating on TRPC5...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27895148/trpc5-regulates-differentiation-through-the-ca2-wnt5a-signal-pathway-in-colorectal-cancer
#8
Zhen Chen, Chunlei Tang, Yaodan Zhu, Mingxu Xie, Dongxu He, Qiongxi Pan, Peng Zhang, Dong Hua, Teng Wang, Linfang Jin, Xiaowei Qi, Yifei Zhu, Xiaoqiang Yao, Jian Jin, Xin Ma
Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca(2+) channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca(2+)]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading to a reduction of cancer differentiation and an increase of cancer cell stemness...
November 28, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27886373/clemizole-hydrochloride-blocks-cardiac-potassium-currents-stably-expressed-in-hek-293-cells
#9
Ling-Jun Jie, Wei-Yin Wu, Gang Li, Guo-Sheng Xiao, Shetuan Zhang, Gui-Rong Li, Yan Wang
BACKGROUND AND PURPOSE: Clemizole, a histamine H1 receptor antagonist has a potential therapeutic effect on hepatitis C infection and also potently inhibits TRPC5 ion channels. The aim of the present study was to investigate whether clemizole blocks cardiac K(+) currents and thus affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch techniques was used to examine the effects of clemizole on hERG channel current, IKs and Kv 1.5 channel current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts...
February 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27854075/benzimidazole-derivative-m084-extends-the-lifespan-of-caenorhabditis-elegans-in-a-daf-16-foxo-dependent-way
#10
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
November 16, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27633915/a-novel-form-of-capsaicin-modified-amygdala-ltd-mediated-by-trpm1
#11
Christine Gebhardt, Oliver von Bohlen Und Halbach, Michael D Hadler, Christian Harteneck, Doris Albrecht
Recently we have shown that capsaicin attenuates the strength of LTP in the lateral amygdala (LA) and demonstrated that this effect is mediated by the transient receptor potential (TRP) channel TRPV1. Here we further show that capsaicin, which is thought to act primarily through TRPV1, modifies long term depression (LTD) in the LA. Yet the application of various TRPV1 antagonists does not reverse this effect and it remains in TRPV1-deficient mice. In addition, voltage gated calcium channels, nitric oxide and CB1 receptors are not involved...
December 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27411851/trpc5-channels-participate-in-pressure-sensing-in-aortic-baroreceptors
#12
On-Chai Lau, Bing Shen, Ching-On Wong, Yung-Wui Tjong, Chun-Yin Lo, Hui-Chuan Wang, Yu Huang, Wing-Ho Yung, Yang-Chao Chen, Man-Lung Fung, John Anthony Rudd, Xiaoqiang Yao
Blood pressure is maintained within a normal physiological range by a sophisticated regulatory mechanism. Baroreceptors serve as a frontline sensor to detect the change in blood pressure. Nerve signals are then sent to the cardiovascular control centre in the brain in order to stimulate baroreflex responses. Here, we identify TRPC5 channels as a mechanical sensor in aortic baroreceptors. In Trpc5 knockout mice, the pressure-induced action potential firings in the afferent nerve and the baroreflex-mediated heart rate reduction are attenuated...
July 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27326323/potential-treatment-for-neuropsychiatry-disorders-with-trpc5-modulators
#13
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
June 9, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27289383/transient-receptor-potential-canonical-4-and-5-proteins-as-targets-in-cancer-therapeutics
#14
REVIEW
Hannah J Gaunt, Naveen S Vasudev, David J Beech
Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca(2+) entry because of the critical roles played by Ca(2+) in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (-)-englerin A...
October 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27196058/hair-cell-mechanotransduction-persists-in-trp-channel-knockout-mice
#15
Xudong Wu, Artur A Indzhykulian, Paul D Niksch, Roxanna M Webber, Miguel Garcia-Gonzalez, Terry Watnick, Jing Zhou, Melissa A Vollrath, David P Corey
Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group...
2016: PloS One
https://www.readbyqxmd.com/read/27165180/transient-receptor-potential-canonical-5-trpc5-protects-against-pain-and-vascular-inflammation-in-arthritis-and-joint-inflammation
#16
Khadija M Alawi, Fiona A Russell, Aisah A Aubdool, Salil Srivastava, Yanira Riffo-Vasquez, Lineu Baldissera, Pratish Thakore, Nurjahan Saleque, Elizabeth S Fernandes, David A Walsh, Susan D Brain
OBJECTIVE: Transient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation has not been previously shown in vivo. We investigated the contribution of TRPC5 in arthritis. METHODS: Male wild-type and TRPC5 knockout (KO) mice were used in a complete Freund's adjuvant (CFA)-induced unilateral arthritis model, assessed over 14 days...
January 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27131740/the-interaction-domains-of-transient-receptor-potential-canonical-trpc-1-4-and-trpc1-5-heteromultimeric-channels
#17
Jongyun Myeong, Juyeon Ko, Chansik Hong, Dongki Yang, Kyu Pil Lee, Ju-Hong Jeon, Insuk So
Transient receptor potential canonical (TRPC) family contains a non-selective cation channel, and four TRPC subunits form a functional tetrameric channel. TRPC4/5 channels form not only the homotetrameric channel but also a heterotetrameric channel with TRPC1. We investigated the interaction domain required for TRPC1/4 or TRPC1/5 heteromultimeric channels using FRET and the patch-clamp technique. TRPC1 only localized at the plasma membrane (PM) when it was coexpressed with TRPC4 or TRPC5. The TRPC1/4 or TRPC1/5 heteromultimeric showed the typical outward rectifying I/V curve...
June 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27129253/transient-receptor-potential-canonical-trpc-orai1-dependent-store-operated-ca2-channels-new-targets-of-aldosterone-in-cardiomyocytes
#18
Jessica Sabourin, Fiona Bartoli, Fabrice Antigny, Ana Maria Gomez, Jean-Pierre Benitah
Store-operated Ca(2+) entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca(2+) influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes...
June 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26969190/sensing-of-redox-status-by-trp-channels
#19
REVIEW
Nozomi Ogawa, Tatsuki Kurokawa, Yasuo Mori
Cellular redox status is maintained by the balance between series of antioxidant systems and production of reactive oxygen/nitrogenous species. Cells utilize this redox balance to mediate diverse physiological functions. Transient receptor potential (TRP) channels are non-selective cation channels that act as biosensors for environmental and noxious stimuli, such as capsaicin and allicin, as well as changes in temperature and conditions inside the cell. TRP channels also have an emerging role as essential players in detecting cellular redox status to regulate cellular signals mediating physiological phenomena...
August 2016: Cell Calcium
https://www.readbyqxmd.com/read/26755577/critical-roles-of-gi-o-proteins-and-phospholipase-c-%C3%AE-1-in-the-activation-of-receptor-operated-trpc4-channels
#20
Dhananjay P Thakur, Jin-bin Tian, Jaepyo Jeon, Jian Xiong, Yu Huang, Veit Flockerzi, Michael X Zhu
Transient Receptor Potential Canonical (TRPC) proteins form nonselective cation channels commonly known to be activated downstream from receptors that signal through phospholipase C (PLC). Although TRPC3/C6/C7 can be directly activated by diacylglycerols produced by PLC breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2), the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. We show here that TRPC4 activation requires coincident stimulation of Gi/o subgroup of G proteins and PLCδ, with a preference for PLCδ1 over PLCδ3, but not necessarily the PLCβ pathway commonly thought to be involved in receptor-operated TRPC activation...
January 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
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