Genomes and Genes
trpc cation channels
Summary: A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
- Dhennin Duthille I, Gautier M, Faouzi M, Guilbert A, Brevet M, Vaudry D, et al. High expression of transient receptor potential channels in human breast cancer epithelial cells and tissues: correlation with pathological parameters. Cell Physiol Biochem. 2011;28:813-22 pubmed publisher..The high expression of TRP channels in tumors suggests the potential of these channels for diagnostic, prognosis and/or therapeutic approaches in human breast ductal adenocarcinoma. ..
- Paez Espinosa E, Murad J, Ting H, Khasawneh F. Mouse transient receptor potential channel 6: role in hemostasis and thrombogenesis. Biochem Biophys Res Commun. 2012;417:853-6 pubmed publisher..Furthermore, TRPC6 may define a new therapeutic target for managing multiple thrombosis-based disorders. ..
- Jeon J, Hong C, Park E, Jeon J, Cho N, Kim I, et al. Selective G?i subunits as novel direct activators of transient receptor potential canonical (TRPC)4 and TRPC5 channels. J Biol Chem. 2012;287:17029-39 pubmed publisher..These findings indicate an essential role of G?(i) proteins as novel activators for TRPC4/5 and reveal the molecular mechanism by which G-proteins activate the channels. ..
- Hong C, Kim J, Jeon J, Wie J, Kwak M, Ha K, et al. Gs cascade regulates canonical transient receptor potential 5 (TRPC5) through cAMP mediated intracellular Ca2+ release and ion channel trafficking. Biochem Biophys Res Commun. 2012;421:105-11 pubmed publisher..In conclusion, these results suggest that the G?(s)-cAMP pathway potentiates the activity of TRPC5 via facilitating intracellular Ca(2+) dynamics and increasing channel trafficking to the plasma membrane. ..
- Cioffi D, Wu S, Chen H, Alexeyev M, St Croix C, Pitt B, et al. Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel. Circ Res. 2012;110:1435-44 pubmed publisher..Orai1 interacts with TRPC4 in the endogenous channel complex, where it controls TRPC1/4 activation and channel permeation characteristics, including calcium selectivity, important for control of endothelial cell barrier function. ..
- Ma X, Cheng K, Wong C, O Neil R, Birnbaumer L, Ambudkar I, et al. Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. Cell Calcium. 2011;50:502-9 pubmed publisher..Vascular tension studies suggest that such an enhanced trafficking of TRPV4-C1 channels may play a role in thapsigargin-induced vascular relaxation in rat small mesenteric arteries. ..
- Antigny F, Girardin N, Frieden M. Transient receptor potential canonical channels are required for in vitro endothelial tube formation. J Biol Chem. 2012;287:5917-27 pubmed publisher..These data showed that TRPC channels are essential for in vitro tubulogenesis, both on endothelial cell line and on primary endothelial cells. ..
- Imai Y, Itsuki K, Okamura Y, Inoue R, Mori M. A self-limiting regulation of vasoconstrictor-activated TRPC3/C6/C7 channels coupled to PI(4,5)P?-diacylglycerol signalling. J Physiol. 2012;590:1101-19 pubmed publisher..These results demonstrate that TRPC3/C6/C7 channels are differentially regulated by depletion of PI(4,5)P?, and that the bimodal signal produced by PLC activation controls these channels in a self-limiting manner. ..
- Storch U, Forst A, Philipp M, Gudermann T, Mederos y Schnitzler M. Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes. J Biol Chem. 2012;287:3530-40 pubmed publisher..These findings suggest a novel regulatory mechanism relying on the expression of TRPC1 and the subsequent formation of heteromeric TRPC channel complexes with reduced calcium permeability, thereby fine-tuning neuronal migration. ..
- Xie J, Cha S, An S, Kuro O M, Birnbaumer L, Huang C. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart. Nat Commun. 2012;3:1238 pubmed publisher..These results provide a new perspective on the pathogenesis of cardiomyopathies and open new avenues for treatment of the disease. ..
- Andrade E, Meotti F, Calixto J. TRPA1 antagonists as potential analgesic drugs. Pharmacol Ther. 2012;133:189-204 pubmed publisher..We also discuss recent advances in the search for new analgesic medicines targeting the TRPA1 channel. ..
- Horinouchi T, Higa T, Aoyagi H, Nishiya T, Terada K, Miwa S. Adenylate cyclase/cAMP/protein kinase A signaling pathway inhibits endothelin type A receptor-operated Ca²? entry mediated via transient receptor potential canonical 6 channels. J Pharmacol Exp Ther. 2012;340:143-51 pubmed publisher..These results suggest that TRPC6 is negatively regulated by the PKA-mediated phosphorylation of Ser28 but not Thr69. ..
- Kang K, Panzano V, Chang E, Ni L, Dainis A, Jenkins A, et al. Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila. Nature. 2011;481:76-80 pubmed publisher..These findings indicate that reducing thermosensitivity can be critical for TRP channel functional diversification, facilitating their use in contexts in which thermal sensitivity can be maladaptive. ..
- Neely G, Keene A, Duchek P, Chang E, Wang Q, Aksoy Y, et al. TrpA1 regulates thermal nociception in Drosophila. PLoS ONE. 2011;6:e24343 pubmed publisher..Therefore, our analysis identifies the channel TRPA1 as a conserved regulator of nociception. ..
- Cordero Morales J, Gracheva E, Julius D. Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proc Natl Acad Sci U S A. 2011;108:E1184-91 pubmed publisher..These findings provide a framework for understanding how restricted changes in TRPA1 sequence account for evolution of physiologically diverse channels, also identifying portable modules that specify thermosensitivity. ..
- Xu S, Zeng B, Daskoulidou N, Chen G, Atkin S, Lukhele B. Activation of TRPC cationic channels by mercurial compounds confers the cytotoxicity of mercury exposure. Toxicol Sci. 2012;125:56-68 pubmed publisher..These results indicate that mercurial compounds are activators for TRPC5 and TRPC4 channels. Blockade of TRPC channels could be a novel strategy for preventing mercury-induced cytotoxicity and neurodevelopment impairment. ..
- Yildirim E, Carey M, Card J, Dietrich A, Flake G, Zhang Y, et al. Severely blunted allergen-induced pulmonary Th2 cell response and lung hyperresponsiveness in type 1 transient receptor potential channel-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2012;303:L539-49 pubmed publisher..Thus we propose that TRPC1 signaling is necessary in lymphocyte biology and in regulation of allergen-induced lung hyperresponsiveness, making TRPC1 a potential target for treatment of immune diseases and asthma. ..
- Numazawa S, Takase M, Ahiko T, Ishii M, Shimizu S, Yoshida T. Possible involvement of transient receptor potential channels in electrophile-induced insulin secretion from RINm5F cells. Biol Pharm Bull. 2012;35:346-54 pubmed
- Sundivakkam P, Freichel M, Singh V, Yuan J, Vogel S, Flockerzi V, et al. The Ca(2+) sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol Pharmacol. 2012;81:510-26 pubmed publisher..Thus, TRPC1 and TRPC4 can interact with STIM1 to form functional store-operated Ca(2+)-entry channels, which are essential for mediating Ca(2+) entry-dependent disruption of the endothelial barrier. ..
- Weissmann N, Sydykov A, Kalwa H, Storch U, Fuchs B, Mederos y Schnitzler M, et al. Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice. Nat Commun. 2012;3:649 pubmed publisher..This mechanism highlights novel pharmacological targets for the treatment of LIRE. ..
- Kim E, Anderson M, Dryer S. Insulin increases surface expression of TRPC6 channels in podocytes: role of NADPH oxidases and reactive oxygen species. Am J Physiol Renal Physiol. 2012;302:F298-307 pubmed publisher..These observations suggest that insulin increases generation of ROS in part through activation of NADPH oxidases, and that this step contributes to modulation of podocyte TRPC6 channels. ..
- Bomben V, Turner K, Barclay T, Sontheimer H. Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas. J Cell Physiol. 2011;226:1879-88 pubmed publisher..These data indicated that TRPC1 channel association with lipid rafts is essential for glioma chemotaxis in response to stimuli, such as EGF. ..
- Kim S, Lee Y, Akitake B, Woodward O, Guggino W, Montell C. Drosophila TRPA1 channel mediates chemical avoidance in gustatory receptor neurons. Proc Natl Acad Sci U S A. 2010;107:8440-5 pubmed publisher..Given that mammalian TRPA1 is required for responding to noxious chemicals, many of which cause pain and injury, our analysis underscores the evolutionarily conserved role for TRPA1 channels in chemical avoidance...
- Ding X, He Z, Zhou K, Cheng J, Yao H, Lu D, et al. Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J Natl Cancer Inst. 2010;102:1052-68 pubmed publisher..In this preclinical model, TRPC6 channels were essential for glioma development via regulation of G2/M phase transition. This study suggests that TRPC6 might be a new target for therapeutic intervention of human glioma. ..
- Kang L, Gao J, Schafer W, Xie Z, Xu X. C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel. Neuron. 2010;67:381-91 pubmed publisher..Importantly, point mutations in the predicted pore region of TRP-4 alter the ion selectivity of the conductance. These results indicate that TRP-4 functions as an essential pore-forming subunit of a native mechanotransduction channel. ..
- Krall P, Canales C, Kairath P, Carmona Mora P, Molina J, Carpio J, et al. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease. PLoS ONE. 2010;5:e12859 pubmed publisher..Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease. ..
- Bousquet S, Monet M, Boulay G. Protein kinase C-dependent phosphorylation of transient receptor potential canonical 6 (TRPC6) on serine 448 causes channel inhibition. J Biol Chem. 2010;285:40534-43 pubmed publisher..Furthermore, knocking down PKC? in A7r5 cells potentiated vasopressin-induced Ca(2+) entry. In summary, we provide evidence that PKC? exerts a negative feedback effect on TRPC6 through the phosphorylation of Ser(448). ..
- Hong J, Li Q, Kim M, Shin D, Feske S, Birnbaumer L, et al. Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells. Traffic. 2011;12:232-45 pubmed publisher..These findings reveal that in addition to Orai1, STIM1 likely regulates other Ca(2+) permeable channels, such as the TRPCs. Both channels contribute to the frequency of [Ca(2+) ] oscillations and thus impact critical cellular functions. ..
- Anantamongkol U, Charoenphandhu N, Wongdee K, Teerapornpuntakit J, Suthiphongchai T, Prapong S, et al. Transcriptome analysis of mammary tissues reveals complex patterns of transporter gene expression during pregnancy and lactation. Cell Biol Int. 2009;34:67-74 pubmed publisher..The present study, therefore, provides information for further investigation of the mechanism of lactation-induced transport adaptation in mammary epithelial cells. ..
- El Hindi S, Reiser J. TRPC channel modulation in podocytes-inching toward novel treatments for glomerular disease. Pediatr Nephrol. 2011;26:1057-64 pubmed publisher..The question now is how to define targets for novel improved therapies. In this review, we summarize critical points around targeting the TRPC6 channel in podocytes. ..
- Jiang L, Gamper N, Beech D. Properties and therapeutic potential of transient receptor potential channels with putative roles in adversity: focus on TRPC5, TRPM2 and TRPA1. Curr Drug Targets. 2011;12:724-36 pubmed..Developing inhibitors of the channels could lead to new agents for a variety of conditions: for example, suppressing unwanted tissue remodeling, inflammation, pain and anxiety, and addressing problems relating to asthma and stroke. ..
- Hu H, Tian J, Zhu Y, Wang C, Xiao R, Herz J, et al. Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs. Pflugers Arch. 2010;459:579-92 pubmed publisher..This selective group of TRPA1-stimulating NSAIDs should provide a structural basis for developing novel ligands that noncovalently interact with TRPA1 channels. ..
- Kobori T, Smith G, Sandford R, Edwardson J. The transient receptor potential channels TRPP2 and TRPC1 form a heterotetramer with a 2:2 stoichiometry and an alternating subunit arrangement. J Biol Chem. 2009;284:35507-13 pubmed publisher..This decoration pattern indicates a TRPP2:TRPC1 subunit stoichiometry of 2:2 and an alternating subunit arrangement. ..
- Zhang P, Yang C, Delay R. Odors activate dual pathways, a TRPC2 and a AA-dependent pathway, in mouse vomeronasal neurons. Am J Physiol Cell Physiol. 2010;298:C1253-64 pubmed publisher..Together, these data from WT and TRPC2(-/-) mice suggest that both DAG and its metabolite, AA, mediate excitatory odor responses in VSNs, by activating two types of channels, a TRPC2 and a separate Ca(2+)-permeable channel...
- Wong C, Sukumar P, Beech D, Yao X. Nitric oxide lacks direct effect on TRPC5 channels but suppresses endogenous TRPC5-containing channels in endothelial cells. Pflugers Arch. 2010;460:121-30 pubmed publisher..The data suggest that nitric oxide is not a direct modulator of homomeric TRPC5 channels but may inhibit endogenous BAEC channels that contain TRPC5. ..
- Wuensch T, Thilo F, Krueger K, Scholze A, Ristow M, Tepel M. High glucose-induced oxidative stress increases transient receptor potential channel expression in human monocytes. Diabetes. 2010;59:844-9 pubmed publisher..05). High d-glucose-induced oxidative stress increases TRP expression and calcium influx in human monocytes, pointing to a novel pathway for increased activation of monocytes and hence atherosclerosis in patients with diabetes. ..
- Yu P, Gu S, Bu J, Du J. TRPC1 is essential for in vivo angiogenesis in zebrafish. Circ Res. 2010;106:1221-32 pubmed publisher..It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis. ..
- Chigurupati S, Venkataraman R, Barrera D, Naganathan A, Madan M, Paul L, et al. Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness. Cancer Res. 2010;70:418-27 pubmed publisher..Collectively, our studies indicate that TRPC6 is a key mediator of tumor growth of GBM in vitro and in vivo and that TRPC6 may be a promising therapeutic target in the treatment of human GBM. ..
- Koitabashi N, Aiba T, Hesketh G, Rowell J, Zhang M, Takimoto E, et al. Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol. 2010;48:713-24 pubmed publisher..Thus PDE5-inhibition blocks TRPC6 channel activation and associated Cn/NFAT activation signaling by PKG-dependent channel phosphorylation. ..
- Wang Z, Wei X, Zhang Y, Ma X, Li B, Zhang S, et al. NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury. Cell Physiol Biochem. 2009;24:619-26 pubmed publisher..Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling. ..
- Cioffi D, Barry C, Stevens T. Store-operated calcium entry channels in pulmonary endothelium: the emerging story of TRPCS and Orai1. Adv Exp Med Biol. 2010;661:137-54 pubmed publisher..Resolving the identity and function of this calcium channel will pave the way for new anti-inflammatory therapeutic targets. ..
- Hauser P, Pippin J, Kaiser C, Krofft R, Brinkkoetter P, Hudkins K, et al. Novel siRNA delivery system to target podocytes in vivo. PLoS ONE. 2010;5:e9463 pubmed publisher..Control rats injected with shamporter coupled to control-siRNA showed no changes. These results show for the first time that siRNA can be delivered efficiently and specifically to podocytes in vivo using an antibody-delivery system. ..
- Al Shawaf E, Naylor J, Taylor H, Riches K, Milligan C, O Regan D, et al. Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2010;30:1453-9 pubmed publisher..Stimulation of calcium-permeable TRPC5-containing channels may be an early event in cellular responses to oxidized phospholipids that couples to cell migration and requires an unidentified G protein-coupled receptor. ..
- Rowell J, Koitabashi N, Kass D. TRP-ing up heart and vessels: canonical transient receptor potential channels and cardiovascular disease. J Cardiovasc Transl Res. 2010;3:516-24 pubmed publisher..This review describes new evidence supporting a pathophysiologic role of these three TRPC channels, and the potential utility of inhibition strategies to treat cardiovascular disease. ..
- Lee K, Yuan J, So I, Worley P, Muallem S. STIM1-dependent and STIM1-independent function of transient receptor potential canonical (TRPC) channels tunes their store-operated mode. J Biol Chem. 2010;285:38666-73 pubmed publisher..Together, these findings indicate that TRPC channels can function as STIM1-dependent and STIM1-independent channels, which increases the versatility of TRPC channel function and their role in receptor-stimulated Ca(2+) influx. ..
- Cheng K, Ong H, Liu X, Ambudkar I. Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion. Adv Exp Med Biol. 2011;704:435-49 pubmed publisher..Major unresolved questions regarding functional interaction between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC channels by store depletion will be discussed. ..
- Santin S, Bullich G, Tazon Vega B, García Maset R, Giménez I, Silva I, et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;6:1139-48 pubmed publisher..We propose a genetic testing algorithm for SRNS based on the age at onset and the familial/sporadic status. Mutation analysis of specific podocyte-genes has a clinical value in all age groups, especially in children. ..
- Nishida M, Watanabe K, Sato Y, Nakaya M, Kitajima N, Ide T, et al. Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition. J Biol Chem. 2010;285:13244-53 pubmed publisher..These results suggest that phosphorylation and functional suppression of TRPC6 underlie prevention of pathological hypertrophy by PDE5 inhibition. ..
- Sun Y, Li Y, Feng S, Li B, Pan Z, Xu C, et al. Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes. Biochem Biophys Res Commun. 2010;394:955-61 pubmed publisher..TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis. ..
- Gross S, Guzmán G, Wissenbach U, Philipp S, Zhu M, Bruns D, et al. TRPC5 is a Ca2+-activated channel functionally coupled to Ca2+-selective ion channels. J Biol Chem. 2009;284:34423-32 pubmed publisher..Our data support the hypothesis that TRPC5 forms Ca(2+)-activated cation channels that are functionally coupled to Ca(2+)-selective ion channels through local Ca(2+) increases beneath the plasma membrane. ..