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https://www.readbyqxmd.com/read/29752403/cryo-em-structure-of-the-cytoplasmic-domain-of-murine-transient-receptor-potential-cation-channel-subfamily-c-member-6-trpc6
#1
Caleigh M Azumaya, Francisco Sierra-Valdez, Julio F Cordero-Morales, Terunaga Nakagawa
The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte and mutations in its cytoplasmic domain cause FSGS in humans. In vitro evaluation of disease-causing mutations in TRPC6 has revealed that these genetic alterations result in abnormal ion channel gating...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29748835/canonical-transient-receptor-potential-channel-3-contributes-to-febrile-seizure-inducing-neuronal-cell-death-and-neuroinflammation
#2
Dan Sun, Hui Ma, Jiehui Ma, Jing Wang, Xiaolong Deng, Chunhui Hu, Xianbo Deng
Febrile seizure (FS) counts as the most common seizures symptom in children undergoing recurrent seizures, posing a high risk to developing subsequent temporal lobe epilepsy. Canonical transient receptor potential channel (TRPC) members are identified as the FS-related genes in hyperthermia prone rats. However, the role of TRPC3 in hyperthermia-induced FS rats remains unclear. In the present study, we investigated whether TRPC3 functionally contributes to the development of FSs. Elevated TRPC3 mRNA and protein levels was detected in hyperthermia-induced FS rats and rat hippocampal neuron cells...
May 10, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29736621/molecular-basis-for-the-sensitivity-of-trp-channels-to-polyunsaturated-fatty-acids
#3
Marc Riehle, Dmitry Tsvetkov, Björn-Oliver Gohlke, Robert Preissner, Christian Harteneck, Maik Gollasch, Bernd Nürnberg
Transient receptor potential (TRP) channels represent a superfamily of unselective cation channels that are subdivided into seven subfamilies based on their sequence homology and differences in gating and functional properties. Little is known about the molecular mechanisms of TRP channel regulation, particularly of the "canonical" TRP (TRPC) subfamily and their activation by polyunsaturated fatty acids (PUFAs). Here, we analyzed the structure-function relationship of Drosophila fruit fly TRPC channels...
May 8, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29733896/discovery-of-feed-forward-regulation-in-l-tryptophan-biosynthesis-and-its-use-in-metabolic-engineering-of-e-coli-for-efficient-tryptophan-bioproduction
#4
Lin Chen, Minliang Chen, Chengwei Ma, An-Ping Zeng
The L-tryptophan (Trp) biosynthesis pathway is highly regulated at multiple levels. The three types of regulations identified so far, namely repression, attenuation, and feedback inhibition have greatly impacted our understanding and engineering of cellular metabolism. In this study, feed-forward regulation is discovered as a novel regulation of this pathway and explored for engineering Escherichia coli for more efficient Trp biosynthesis. Specifically, indole glycerol phosphate synthase (IGPS) of the multifunctional enzyme TrpC from E...
May 4, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29733572/synergistic-effect-of-transient-receptor-potential-antagonist-and-amiloride-against-maitotoxin-induced-calcium-increase-and-cytotoxicity-in-human-neuronal-stem-cells
#5
Andrea Boente Juncal, Carmen Vale, Amparo Alfonso, Luis M Botana
Maitotoxins (MTX) are among the most potent marine toxins identified to date causing cell death trough massive calcium influx. However, the exact mechanism for the MTX-induced calcium entry and cytotoxicity is still unknown. In this work, the effect of MTX-1 on the cytosolic free calcium concentration and cellular viability of human neuronal stem cells was evaluated. MTX elicited a concentration-dependent decrease in cell viability which was already evident after 1 hour of treatment with 0.25 nM MTX; however at a concentration of 0...
May 7, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29726814/structure-of-the-human-lipid-gated-cation-channel-trpc3
#6
Chen Fan, Wooyoung Choi, Weinan Sun, Juan Du, Wei Lu
The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels...
May 4, 2018: ELife
https://www.readbyqxmd.com/read/29717981/electron-cryo-microscopy-structure-of-the-canonical-trpc4-ion-channel
#7
Deivanayagabarathy Vinayagam, Thomas Mager, Amir Apelbaum, Arne Bothe, Felipe Merino, Oliver Hofnagel, Christos Gatsogiannis, Stefan Raunser
Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3...
May 2, 2018: ELife
https://www.readbyqxmd.com/read/29700422/structure-of-the-receptor-activated-human-trpc6-and-trpc3-ion-channels
#8
Qinglin Tang, Wenjun Guo, Li Zheng, Jing-Xiang Wu, Meng Liu, Xindi Zhou, Xiaolin Zhang, Lei Chen
TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid second messenger. TRPC6 and TRPC3 are involved in many physiological processes and implicated in human genetic diseases. Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high-affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 Å resolution...
April 26, 2018: Cell Research
https://www.readbyqxmd.com/read/29660945/trpc1-null-exacerbates-memory-deficit-and-apoptosis-induced-by-amyloid-%C3%AE
#9
Mengzhu Li, Enjie Liu, Qiuzhi Zhou, Shihong Li, Xin Wang, Yanchao Liu, Lin Wang, Dongsheng Sun, Jinwang Ye, Yuan Gao, Xifei Yang, Jianjun Liu, Ying Yang, Jian-Zhi Wang
The transient receptor potential cation (TRPC) channels are widely expressed in nervous system but their functions remain largely unclear. Here, we found that TRPC1 deletion did not affect learning and memory in physiological conditions, while it aggravated learning and memory deficits induced by amyloid-β (Aβ), the major component of the senile plaques observed in the brains of Alzheimer's disease (AD). Further studies demonstrated that TRPC1 deletion did not affect cell apoptosis in physiological condition, but it exacerbated the Aβ-induced cell death in mouse hippocampus...
April 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29624776/trpc3-overexpression-and-intervention-in-airway-smooth-muscle-of-ovalbumin-induced-hyperresponsiveness-and-remodeling
#10
Bo-Ming Xu, Jia-Hua Zhang, Jia-Ling Wang, Jun-Hua Xiao
Transient receptor potential canonical channel 3 (TRPC3) proteins function as non-voltage-gated Ca2+ -permeable channels and play divergent roles in many processes of pathophysiology. The purpose of this study was to determine the relationship between TRPC3 expression and airway hyperresponsiveness and remodeling in ovalbumin-induced asthmatic Kunming mice. Mice were sensitized and challenged by ovalbumin to establish asthmatic model. Hematoxylin-eosin staining, hydroxyproline assay and isometric tracheal ring force measurement were used to evaluate airway remodeling and hyperresponsiveness in asthmatic mice...
April 6, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29623030/on-the-role-of-store-operated-calcium-entry-in-acute-and-chronic-neurodegenerative-diseases
#11
REVIEW
Agnese Secondo, Giacinto Bagetta, Diana Amantea
In both excitable and non-excitable cells, calcium (Ca2+ ) signals are maintained by a highly integrated process involving store-operated Ca2+ entry (SOCE), namely the opening of plasma membrane (PM) Ca2+ channels following the release of Ca2+ from intracellular stores. Upon depletion of Ca2+ store, the stromal interaction molecule (STIM) senses Ca2+ level reduction and migrates from endoplasmic reticulum (ER)-like sites to the PM where it activates the channel proteins Orai and/or the transient receptor potential channels (TRPC) prompting Ca2+ refilling...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29618985/the-complex-role-of-store-operated-calcium-entry-pathways-and-related-proteins-in-the-function-of-cardiac-skeletal-and-vascular-smooth-muscle-cells
#12
REVIEW
Javier Avila-Medina, Isabel Mayoral-Gonzalez, Alejandro Dominguez-Rodriguez, Isabel Gallardo-Castillo, Juan Ribas, Antonio Ordoñez, Juan A Rosado, Tarik Smani
Cardiac, skeletal, and smooth muscle cells shared the common feature of contraction in response to different stimuli. Agonist-induced muscle's contraction is triggered by a cytosolic free Ca2+ concentration increase due to a rapid Ca2+ release from intracellular stores and a transmembrane Ca2+ influx, mainly through L-type Ca2+ channels. Compelling evidences have demonstrated that Ca2+ might also enter through other cationic channels such as Store-Operated Ca2+ Channels (SOCCs), involved in several physiological functions and pathological conditions...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29599657/phototransduction-in-retinal-ganglion-cells
#13
REVIEW
Peter B Detwiler
The mammalian retina contains a small number of retinal ganglion cells that express melanopsin, a retinal based visual pigment, and generate a depolarizing response to light in the absence of rod and cone driven synaptic input; hence they are referred to as intrinsically photosensitive retinal ganglion cells (ipRGCs). They have been shown to be comprised of a number of sub-types and to provide luminance information that participates primarily in a variety of non-imaging forming visual functions. Here I review what is currently known about the cascade of events that couple the photoisomerization of melanopsin to the opening of a non-selective cation channel...
March 2018: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/29578059/the-effect-of-the-electrophilic-fatty-acid-nitro-oleic-acid-on-trp-channel-function-in-sensory-neurons
#14
REVIEW
Jonathan M Beckel, William C de Groat
Nitro-oleic acid (NO2 -OA) and related nitroalkenes are electrophilic fatty acid derivatives that are present in normal tissues at nanomolar concentrations and can increase significantly during inflammation. These substances can suppress multiple intracellular signaling pathways contributing to inflammation by reversible Michael addition reactions with nucleophilic residues such as cysteine and histidine leading to post-translational modification of proteins. NO2 -OA also can influence inflammation and pain by acting on transient receptor potential (TRP) channels in primary sensory neurons...
March 22, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29574924/the-effects-of-transient-receptor-potential-channel-trpc-on-airway-smooth-muscle-cell-isolated-from-asthma-model-mice
#15
Xiaoyu Zhang, Zhixin Zhao, Lijun Ma, Yali Guo, Xiaosu Li, Limin Zhao, Cuijie Tian, Xueyi Tang, Dongjun Cheng, Zhuochang Chen, Luoxian Zhang
This study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+ ) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non- asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects...
March 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29570903/trpc1-3-6-inhibition-attenuates-the-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-gastric-cancer-via-the-ras-raf1-erk-signaling-pathway
#16
Pengbo Ge, Linting Wei, Mingkai Zhang, Baoguang Hu, Kai Wang, Yanbin Li, Shuaichen Liu, Jianping Wang, Yuming Li
Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-β1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca2+ entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-β1-induced EMT of GC and to investigate the potential mechanisms...
March 23, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29560783/trpc6-and-trpc4-heteromultimerization-mediates-store-depletion-activated-ncx1-reversal-in-proliferative-vascular-smooth-muscle-cells
#17
Bin Zhang, Bei Liu, Carolyn M Roos, Michael A Thompson, Y S Prakash, Jordan D Miller, Rui-Wei Guo
Store depletion has been shown to induce Ca2+ entry by Na+/Ca+ exchange (NCX) 1 reversal in proliferative vascular smooth muscle cells (VSMCs). The study objective was to investigate the role of transient receptor potential canonical (TRPC) channels in store depletion and NCX1 reversal in proliferative VSMCs. In cultured VSMCs, expressing TRPC1, TRPC4, and TRPC6, the removal of extracellular Na+ was followed by a significant increase of cytosolic Ca2+ concentration that was inhibited by KBR, a selective NCX1 inhibitor...
March 21, 2018: Channels
https://www.readbyqxmd.com/read/29556099/an-optically-controlled-probe-identifies-lipid-gating-fenestrations-within-the-trpc3-channel
#18
Michaela Lichtenegger, Oleksandra Tiapko, Barbora Svobodova, Thomas Stockner, Toma N Glasnov, Wolfgang Schreibmayer, Dieter Platzer, Gema Guedes de la Cruz, Sarah Krenn, Romana Schober, Niroj Shrestha, Rainer Schindl, Christoph Romanin, Klaus Groschner
Transient receptor potential canonical (TRPC) channels TRPC3, TRPC6 and TRPC7 are able to sense the lipid messenger diacylglycerol (DAG). The DAG-sensing and lipid-gating processes in these ion channels are still unknown. To gain insights into the lipid-sensing principle, we generated a DAG photoswitch, OptoDArG, that enabled efficient control of TRPC3 by light. A structure-guided mutagenesis screen of the TRPC3 pore domain unveiled a single glycine residue behind the selectivity filter (G652) that is exposed to lipid through a subunit-joining fenestration...
March 19, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29535613/trpc1-channels-are-expressed-in-pyramidal-neurons-and-in-a-subset-of-somatostatin-interneurons-in-the-rat-neocortex
#19
Juan R Martinez-Galan, Ana Verdejo, Elena Caminos
Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC) and/or store-operated calcium (SOC) channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP) superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs) and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29501506/do-trpc-channels-support-working-memory-comparing-modulations-of-trpc-channels-and-working-memory-through-g-protein-coupled-receptors-and-neuromodulators
#20
REVIEW
Antonio Reboreda, Frederik M Theissen, Maria J Valero-Aracama, Alberto Arboit, Mihaela A Corbu, Motoharu Yoshida
Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks...
March 1, 2018: Behavioural Brain Research
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