Transient receptor potential (TRP) channel function in the reproductive axis

The transient receptor potential (TRP) cation channel superfamily comprises more than 50 channels that play crucial roles in physiological processes. TRP channels are responsive to several exogenous and endogenous biomolecules, with aldehydes emerging as a TRP channel trigger contributing to a cellular cascade that can lead to disease pathophysiology. The body is not only exposed to exogenous aldehydes via tobacco products or alcoholic beverages, but also to endogenous aldehydes triggered by lipid peroxidation. In response to lipid peroxidation from inflammation or organ injury, polyunsaturated fatty acids undergo lipid peroxidation to aldehydes, such as 4-hydroxynonenal. Reactive aldehydes activate TRP channels via aldehyde-induced protein adducts, leading to the release of pro-inflammatory mediators driving the pathophysiology caused by cellular injury, including inflammatory pain and organ reperfusion injury. Recent studies have outlined how aldehyde dehydrogenase 2 protects against aldehyde toxicity through the clearance of toxic aldehydes, indicating that targeting the endogenous aldehyde metabolism may represent a novel treatment strategy. An addition approach can involve targeting specific TRP channel regions to limit the triggering of a cellular cascade induced by aldehydes. In this review, we provide a comprehensive summary of aldehydes, TRP channels, and their interactions, as well as their role in pathological conditions and the different therapeutical treatment options.

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Functional characterization of transient receptor potential channels in mouse urothelial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00599.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. F692-F701 ◽

Cited By ~ 101

Author(s):

Wouter Everaerts ◽

Joris Vriens ◽

Grzegorz Owsianik ◽

Giovanni Appendino ◽

Thomas Voets ◽

...

Keyword(s):

Plasma Membrane ◽

Patch Clamp ◽

Calcium Imaging ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Functional Expression ◽

Sensory Function ◽

Trp Channel ◽

Urothelial Cells ◽

Transient Receptor

The bladder urothelium is currently believed to be a sensory structure, contributing to mechano- and chemosensation in the bladder. Transient receptor potential (TRP) cation channels act as polymodal sensors and may underlie some of the receptive properties of urothelial cells. However, the exact TRP channel expression profile of urothelial cells is unclear. In this study, we have performed a systematic analysis of the molecular and functional expression of various TRP channels in mouse urothelium. Urothelial cells from control and trpv4−/− mice were isolated, cultured (12–48 h), and used for quantitative real-time PCR, immunocytochemistry, calcium imaging, and whole cell patch-clamp experiments. At the mRNA level, TRPV4, TRPV2, and TRPM7 were the most abundantly expressed TRP genes. Immunohistochemistry showed a clear expression of TRPV4 in the plasma membrane, whereas TRPV2 was more prominent in the cytoplasm. TRPM7 was detected in the plasma membrane as well as cytoplasmic vesicles. Calcium imaging and patch-clamp experiments using TRP channel agonists and antagonists provided evidence for the functional expression of TRPV4, TRPV2, and TRPM7 but not of TRPA1, TRPV1, and TRPM8. In conclusion, we have demonstrated functional expression of TRPV4, TRPV2, and TRPM7 in mouse urothelial cells. These channels may contribute to the (mechano)sensory function of the urothelial layer and represent potential targets for the treatment of bladder dysfunction.

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Responses to transient receptor potential (TRP) channel agonists in Chlamydomonas reinhardtii

Biology Open ◽

10.1242/bio.053140 ◽

2020 ◽

Vol 9 (7) ◽

pp. bio053140

Author(s):

Mamoru Wada ◽

Itaru Kaizuka ◽

Kenjiro Yoshimura

Keyword(s):

Chlamydomonas Reinhardtii ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Trp Channel ◽

Transient Receptor

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The use of transient receptor potential (TRP) channel agonist in promoting bone regeneration and anti-osteoporosis

African Journal of Pharmacy and Pharmacology ◽

10.5897/ajpp10.272 ◽

2011 ◽

Vol 5 (4) ◽

pp. 559-560

Author(s):

Zhao-Gui Zhang

Keyword(s):

Bone Regeneration ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Trp Channel ◽

Transient Receptor ◽

Channel Agonist

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Human transient receptor potential (TRP) channel expression profiling in carcinogenesis

The International Journal of Developmental Biology ◽

10.1387/ijdb.150232dg ◽

2015 ◽

Vol 59 (7-8-9) ◽

pp. 399-406 ◽

Cited By ~ 15

Author(s):

Michela Bernardini ◽

Alessandra Fiorio Pla ◽

Natalia Prevarskaya ◽

Dimitra Gkika

Keyword(s):

Expression Profiling ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Trp Channel ◽

Channel Expression ◽

Transient Receptor

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Structure of the human PKD1-PKD2 complex

Science ◽

10.1126/science.aat9819 ◽

2018 ◽

Vol 361 (6406) ◽

pp. eaat9819 ◽

Cited By ~ 60

Author(s):

Qiang Su ◽

Feizhuo Hu ◽

Xiaofei Ge ◽

Jianlin Lei ◽

Shengqiang Yu ◽

...

Keyword(s):

Transient Receptor Potential ◽

Complex Structure ◽

Transmembrane Helix ◽

Receptor Potential ◽

Trp Channel ◽

Cryo Electron Microscopy ◽

Disease Mechanisms ◽

Autosomal Dominant Polycystic Kidney ◽

Transient Receptor ◽

Positively Charged

Mutations in two genes, PKD1 and PKD2, account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins.

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The nonselective cation channel TRPV4 inhibits angiotensin II receptors

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014325 ◽

2020 ◽

Vol 295 (29) ◽

pp. 9986-9997

Author(s):

Nicholas W. Zaccor ◽

Charlotte J. Sumner ◽

Solomon H. Snyder

Keyword(s):

Angiotensin Ii ◽

G Protein ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Trp Channel ◽

Luciferase Assay ◽

Transient Receptor Potential Vanilloid ◽

Dependent Manner ◽

Transient Receptor

G-protein–coupled receptors (GPCRs) are a ubiquitously expressed family of receptor proteins that regulate many physiological functions and other proteins. They act through two dissociable signaling pathways: the exchange of GDP to GTP by linked G-proteins and the recruitment of β-arrestins. GPCRs modulate several members of the transient receptor potential (TRP) channel family of nonselective cation channels. How TRP channels reciprocally regulate GPCR signaling is less well-explored. Here, using an array of biochemical approaches, including immunoprecipitation and fluorescence, calcium imaging, phosphate radiolabeling, and a β-arrestin–dependent luciferase assay, we characterize a GPCR–TRP channel pair, angiotensin II receptor type 1 (AT1R), and transient receptor potential vanilloid 4 (TRPV4), in primary murine choroid plexus epithelial cells and immortalized cell lines. We found that AT1R and TRPV4 are binding partners and that activation of AT1R by angiotensin II (ANGII) elicits β-arrestin–dependent inhibition and internalization of TRPV4. Activating TRPV4 with endogenous and synthetic agonists inhibited angiotensin II–mediated G-protein–associated second messenger accumulation, AT1R receptor phosphorylation, and β-arrestin recruitment. We also noted that TRPV4 inhibits AT1R phosphorylation by activating the calcium-activated phosphatase calcineurin in a Ca2+/calmodulin–dependent manner, preventing β-arrestin recruitment and receptor internalization. These findings suggest that when TRP channels and GPCRs are co-expressed in the same tissues, many of these channels can inhibit GPCR desensitization.

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

The Journal of Cell Biology ◽

10.1083/jcb.200508030 ◽

2005 ◽

Vol 171 (4) ◽

pp. 685-694 ◽

Cited By ~ 28

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.

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