scholarly journals Ciliary Genes in Renal Cystic Diseases

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 907 ◽  
Author(s):  
Anna Adamiok-Ostrowska ◽  
Agnieszka Piekiełko-Witkowska
Keyword(s):  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Apical Cell ◽  
Receptor Potential ◽  
Renal Diseases ◽  
Special Focus ◽  
Type I ◽  
Altered Expression ◽  
Transient Receptor ◽  
The Impact

Cilia are microtubule-based organelles, protruding from the apical cell surface and anchoring to the cytoskeleton. Primary (nonmotile) cilia of the kidney act as mechanosensors of nephron cells, responding to fluid movements by triggering signal transduction. The impaired functioning of primary cilia leads to formation of cysts which in turn contribute to development of diverse renal diseases, including kidney ciliopathies and renal cancer. Here, we review current knowledge on the role of ciliary genes in kidney ciliopathies and renal cell carcinoma (RCC). Special focus is given on the impact of mutations and altered expression of ciliary genes (e.g., encoding polycystins, nephrocystins, Bardet-Biedl syndrome (BBS) proteins, ALS1, Oral-facial-digital syndrome 1 (OFD1) and others) in polycystic kidney disease and nephronophthisis, as well as rare genetic disorders, including syndromes of Joubert, Meckel-Gruber, Bardet-Biedl, Senior-Loken, Alström, Orofaciodigital syndrome type I and cranioectodermal dysplasia. We also show that RCC and classic kidney ciliopathies share commonly disturbed genes affecting cilia function, including VHL (von Hippel-Lindau tumor suppressor), PKD1 (polycystin 1, transient receptor potential channel interacting) and PKD2 (polycystin 2, transient receptor potential cation channel). Finally, we discuss the significance of ciliary genes as diagnostic and prognostic markers, as well as therapeutic targets in ciliopathies and cancer.

scholarly journals TRPA1: a molecular view

2019 ◽  
Vol 121 (2) ◽  
pp. 427-443 ◽  
Author(s):  
Jannis E. Meents ◽  
Cosmin I. Ciotu ◽  
Michael J. M. Fischer
Keyword(s):  
Molecular Structure ◽  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Special Focus ◽  
Remarkable Feature ◽  
Modulatory Sites ◽  
Transient Receptor ◽  
Major Target ◽  
Made In

The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed in pain-sensing neurons and other tissues and has become a major target in the development of novel pharmaceuticals. A remarkable feature of the channel is its long list of activators, many of which we are exposed to in daily life. Many of these agonists induce pain and inflammation, making TRPA1 a major target for anti-inflammatory and analgesic therapies. Studies in human patients and in experimental animals have confirmed an important role for TRPA1 in a number of pain conditions. Over the recent years, much progress has been made in elucidating the molecular structure of TRPA1 and in discovering binding sites and modulatory sites of the channel. Because the list of published mutations and important molecular sites is steadily growing and because it has become difficult to see the forest for the trees, this review aims at summarizing the current knowledge about TRPA1, with a special focus on the molecular structure and the known binding or gating sites of the channel.

scholarly journals Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

2020 ◽  
Vol 100 (2) ◽  
pp. 725-803 ◽  
Author(s):  
Karel Talavera ◽  
Justyna B. Startek ◽  
Julio Alvarez-Collazo ◽  
Brett Boonen ◽  
Yeranddy A. Alpizar ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Cellular Damage ◽  
Mechanical Stimuli ◽  
Amino Acid Residues ◽  
Nonselective Cation Channels ◽  
Organ Systems ◽  
Complex Regulation ◽  
Transient Receptor

The transient receptor potential ankyrin (TRPA) channels are Ca2+-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH2 terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This includes a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel and many other chemically unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat, and mechanical stimuli, and its function is modulated by multiple factors, including Ca2+, trace metals, pH, and reactive oxygen, nitrogen, and carbonyl species. TRPA1 is involved in acute and chronic pain as well as inflammation, plays key roles in the pathophysiology of nearly all organ systems, and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties, and complex regulation to its roles in multiple pathophysiological conditions.

scholarly journals Dissecting independent channel and scaffolding roles of the Drosophila transient receptor potential channel

2005 ◽  
Vol 171 (4) ◽  
pp. 685-694 ◽  
Author(s):  
Tao Wang ◽  
Yuchen Jiao ◽  
Craig Montell
Keyword(s):  
Cell Death ◽  
Retinal Degeneration ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Loss Of Function ◽  
Visual Transduction ◽  
Channel Function ◽  
Transient Receptor ◽  
The Impact

Drosophila transient receptor potential (TRP) serves dual roles as a cation channel and as a molecular anchor for the PDZ protein, INAD (inactivation no afterpotential D). Null mutations in trp cause impairment of visual transduction, mislocalization of INAD, and retinal degeneration. However, the impact of specifically altering TRP channel function is not known because existing loss-of-function alleles greatly reduce protein expression. In the current study we describe the isolation of a set of new trp alleles, including trp14 with an amino acid substitution juxtaposed to the TRP domain. The trp14 flies stably express TRP and display normal molecular anchoring, but defective channel function. Elimination of the anchoring function alone in trpΔ1272, had minor effects on retinal morphology whereas disruption of channel function caused profound light-induced cell death. This retinal degeneration was greatly suppressed by elimination of the Na+/Ca2+ exchanger, CalX, indicating that the cell death was due primarily to deficient Ca2+ entry rather than disruption of the TRP-anchoring function.

scholarly journals Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162543 ◽  
Author(s):  
Katsuya Ohbuchi ◽  
Yoshikazu Mori ◽  
Kazuo Ogawa ◽  
Eiji Warabi ◽  
Masahiro Yamamoto ◽  
...  
Keyword(s):  
Detailed Analysis ◽  
Transient Receptor Potential ◽  
Computational Study ◽  
Receptor Potential ◽  
Binding Mode ◽  
Transient Receptor Potential Vanilloid ◽  
Type I ◽  
Transient Receptor

scholarly journals Coordinated waves of actomyosin flow and apical cell constriction immediately after wounding

2013 ◽  
Vol 202 (2) ◽  
pp. 365-379 ◽  
Author(s):  
Marco Antunes ◽  
Telmo Pereira ◽  
João V. Cordeiro ◽  
Luis Almeida ◽  
Antonio Jacinto
Keyword(s):  
Actin Filament ◽  
Transient Receptor Potential ◽  
Apical Cell ◽  
Leading Edge ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Wound Response ◽  
Epithelial Wound Healing ◽  
Cytoskeleton Remodeling ◽  
Transient Receptor

Epithelial wound healing relies on tissue movements and cell shape changes. Our work shows that, immediately after wounding, there was a dramatic cytoskeleton remodeling consisting of a pulse of actomyosin filaments that assembled in cells around the wound edge and flowed from cell to cell toward the margin of the wound. We show that this actomyosin flow was regulated by Diaphanous and ROCK and that it elicited a wave of apical cell constriction that culminated in the formation of the leading edge actomyosin cable, a structure that is essential for wound closure. Calcium signaling played an important role in this process, as its intracellular concentration increased dramatically immediately after wounding, and down-regulation of transient receptor potential channel M, a stress-activated calcium channel, also impaired the actomyosin flow. Lowering the activity of Gelsolin, a known calcium-activated actin filament–severing protein, also impaired the wound response, indicating that cleaving the existing actin filament network is an important part of the cytoskeleton remodeling process.

scholarly journals Molecular Basis of TRPA1 Regulation in Nociceptive Neurons. A Review

2017 ◽  
pp. 425-439 ◽  
Author(s):  
A. KÁDKOVÁ ◽  
V. SYNYTSYA ◽  
J. KRUSEK ◽  
L. ZÍMOVÁ ◽  
V. VLACHOVÁ
Keyword(s):  
Molecular Basis ◽  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Nociceptive Response ◽  
Nociceptive Neurons ◽  
Physiological Relevance ◽  
Wide Range ◽  
Transient Receptor

Transient receptor potential A1 (TRPA1) is an excitatory ion channel that functions as a cellular sensor, detecting a wide range of proalgesic agents such as environmental irritants and endogenous products of inflammation and oxidative stress. Topical application of TRPA1 agonists produces an acute nociceptive response through peripheral release of neuropeptides, purines and other transmitters from activated sensory nerve endings. This, in turn, further regulates TRPA1 activity downstream of G-protein and phospholipase C-coupled signaling cascades. Despite the important physiological relevance of such regulation leading to nociceptor sensitization and consequent pain hypersensitivity, the specific domains through which TRPA1 undergoes post-translational modifications that affect its activation properties are yet to be determined at a molecular level. This review aims at providing an account of our current knowledge on molecular basis of regulation by neuronal inflammatory signaling pathways that converge on the TRPA1 channel protein and through modification of its specific residues influence the extent to which this channel may contribute to pain.

scholarly journals TRPing on Cell Swelling - TRPV4 Senses It

2021 ◽  
Vol 12 ◽  
Author(s):  
Trine L. Toft-Bertelsen ◽  
Nanna MacAulay
Keyword(s):  
Cell Volume ◽  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Cell Swelling ◽  
Transient Receptor Potential Vanilloid ◽  
Volume Changes ◽  
Channel Activation ◽  
Volume Increase ◽  
Transient Receptor

The transient receptor potential vanilloid 4 channel (TRPV4) is a non-selective cation channel that is widely expressed and activated by a range of stimuli. Amongst these stimuli, changes in cell volume feature as a prominent regulator of TRPV4 activity with cell swelling leading to channel activation. In experimental settings based on abrupt introduction of large osmotic gradients, TRPV4 activation requires co-expression of an aquaporin (AQP) to facilitate such cell swelling. However, TRPV4 readily responds to cell volume increase irrespectively of the molecular mechanism underlying the cell swelling and can, as such, be considered a sensor of increased cell volume. In this review, we will discuss the proposed events underlying the molecular coupling from cell swelling to channel activation and present the evidence of direct versus indirect swelling-activation of TRPV4. With this summary of the current knowledge of TRPV4 and its ability to sense cell volume changes, we hope to stimulate further experimental efforts in this area of research to clarify TRPV4’s role in physiology and pathophysiology.

scholarly journals TRP Channels as Drug Targets to Relieve Itch

2018 ◽  
Vol 11 (4) ◽  
pp. 100 ◽  
Author(s):  
Zili Xie ◽  
Hongzhen Hu
Keyword(s):  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Protective Role ◽  
Chronic Itch ◽  
Transient Receptor

Although acute itch has a protective role by removing irritants to avoid further damage, chronic itch is debilitating, significantly impacting quality of life. Over the past two decades, a considerable amount of stimulating research has been carried out to delineate mechanisms of itch at the molecular, cellular, and circuit levels. There is growing evidence that transient receptor potential (TRP) channels play important roles in itch signaling. The purpose of this review is to summarize our current knowledge about the role of TRP channels in the generation of itch under both physiological and pathological conditions, thereby identifying them as potential drug targets for effective anti-itch therapies.

scholarly journals Transient receptor potential channel 6 regulates abnormal cardiac S-nitrosylation in Duchenne muscular dystrophy

2017 ◽  
Vol 114 (50) ◽  
pp. E10763-E10771 ◽  
Author(s):  
Heaseung Sophia Chung ◽  
Grace E. Kim ◽  
Ronald J. Holewinski ◽  
Vidya Venkatraman ◽  
Guangshuo Zhu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
The Impact

Duchenne muscular dystrophy (DMD) is an X-linked disorder with dystrophin loss that results in skeletal and cardiac muscle weakening and early death. Loss of the dystrophin–sarcoglycan complex delocalizes nitric oxide synthase (NOS) to alter its signaling, and augments mechanosensitive intracellular Ca2+ influx. The latter has been coupled to hyperactivation of the nonselective cation channel, transient receptor potential canonical channel 6 (Trpc6), in isolated myocytes. As Ca2+ also activates NOS, we hypothesized that Trpc6 would help to mediate nitric oxide (NO) dysregulation and that this would be manifest in increased myocardial S-nitrosylation, a posttranslational modification increasingly implicated in neurodegenerative, inflammatory, and muscle disease. Using a recently developed dual-labeling proteomic strategy, we identified 1,276 S-nitrosylated cysteine residues [S-nitrosothiol (SNO)] on 491 proteins in resting hearts from a mouse model of DMD (dmdmdx:utrn+/−). These largely consisted of mitochondrial proteins, metabolic regulators, and sarcomeric proteins, with 80% of them also modified in wild type (WT). S-nitrosylation levels, however, were increased in DMD. Genetic deletion of Trpc6 in this model (dmdmdx:utrn+/−:trpc6−/−) reversed ∼70% of these changes. Trpc6 deletion also ameliorated left ventricular dilation, improved cardiac function, and tended to reduce fibrosis. Furthermore, under catecholamine stimulation, which also increases NO synthesis and intracellular Ca2+ along with cardiac workload, the hypernitrosylated state remained as it did at baseline. However, the impact of Trpc6 deletion on the SNO proteome became less marked. These findings reveal a role for Trpc6-mediated hypernitrosylation in dmdmdx:utrn+/− mice and support accumulating evidence that implicates nitrosative stress in cardiac and muscle disease.

Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

2010 ◽  
Vol 298 (1) ◽  
pp. H171-H178 ◽  
Author(s):  
N. B. Bishara ◽  
H. Ding
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Current Data ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Transient Receptor ◽  
The Impact ◽  
Aortic Endothelial

Hyperglycemia is a major risk factor for endothelial dysfunction and vascular disease, and in the current study, the link to glucose-induced abnormal intracellular Ca2+ (Cai2+) homeostasis was explored in bovine aortic endothelial cells in high glucose (HG; 25 mmol/l) versus low glucose (LG; 5.5 mmol/l; control). Transient receptor potential 1 (TRPC1) ion channel protein, but not TRPC3, TRPC4, or TRPC6 expression, was significantly increased in HG versus LG at 72 h. HG for 4, 24, and 72 h did not change basal Cai2+ or ATP-induced Cai2+ release; however, the amplitude of sustained Cai2+ was significantly increased at 24 and 72 h and reduced by low concentration of the putative, but nonspecific, TRPC blockers, gadolinium, SKF-96365, and 2-aminoethoxydiphenyl borate. Treatment with TRPC1 antisense significantly reduced TRPC1 protein expression and ATP-induced Ca2+ entry in bovine aortic endothelial cells. Although the link between HG-induced changes in TRPC1 expression, enhanced Ca2+ entry, and endothelial dysfunction require further study, the current data are suggestive that targeting these pathways may reduce the impact of HG on endothelial function.

Sign in / Sign up

Export Citation Format

Share Document