Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular mechanism of TRP channels.

ABSTRACT: Transient receptor potential (TRP) channels are cellular sensors for a wide spectrum of physical and chemical stimuli. They are involved in the formation of sight, hearing, touch, smell, taste, temperature, and pain sensation. TRP channels also play fundamental roles in cell signaling and allow the host cell to respond to benign or harmful environmental changes. As TRP channel activation is controlled by very diverse processes and, in many cases, exhibits complex polymodal properties, understanding how each TRP channel responds to its unique forms of activation energy is both crucial and challenging. The past two decades witnessed significant advances in understanding the molecular mechanisms that underlie TRP channels activation. This review focuses on our current understanding of the molecular determinants for TRP channel activation.

SUBMITTER: Zheng J

PROVIDER: S-EPMC3775668 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Molecular mechanism of TRP channels.

Zheng Jie J

Comprehensive Physiology 20130101 1

Transient receptor potential (TRP) channels are cellular sensors for a wide spectrum of physical and chemical stimuli. They are involved in the formation of sight, hearing, touch, smell, taste, temperature, and pain sensation. TRP channels also play fundamental roles in cell signaling and allow the host cell to respond to benign or harmful environmental changes. As TRP channel activation is controlled by very diverse processes and, in many cases, exhibits complex polymodal properties, understand ...[more]

PMID: 23720286

Similar Datasets

TRP Channels as Molecular Targets to Relieve Cancer Pain.

Project description:Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment.

| S-EPMC8774023 | biostudies-literature

Forcing open TRP channels: Mechanical gating as a unifying activation mechanism.

Project description:Transient receptor potential (TRP) proteins are cation channels that comprise a superfamily of molecular sensors that enable animals to detect a wide variety of environmental stimuli. This versatility enables vertebrate and invertebrate TRP channels to function in a diversity of senses, ranging from vision to taste, smell, touch, hearing, proprioception and thermosensation. Moreover, many individual TRP channels are activated through a surprising range of sensory stimuli. The multitasking nature of TRP channels raises the question as to whether seemingly disparate activators gate TRPs through common strategies. In this regard, a recent major advance is the discovery that a phospholipase C (PLC)-dependent signaling cascade activates the TRP channels in Drosophila photoreceptor cells through generation of force in the lipid-bilayer. The premise of this review is that mechanical force is a unifying, common strategy for gating TRP channels. In addition to several TRP channels that function in mechanosensation and are gated by force applied to the cells, changes in temperature or alterations in the concentration of lipophilic second messengers through stimulation of signaling cascades, cause architectural modifications of the cell membrane, which in turn activate TRP channels through mechanical force. Consequently, TRPs are capable of functioning as stretch-activated channels, even in cases in which the stimuli that initiate the signaling cascades are not mechanical. We propose that most TRPs are actually mechanosensitive channels (MSCs), which undergo conformational changes in response to tension imposed on the lipid bilayer, resulting in channel gating.

| S-EPMC4441759 | biostudies-literature

Comparative sequence analysis suggests a conserved gating mechanism for TRP channels.

Project description:The transient receptor potential (TRP) channel superfamily plays a central role in transducing diverse sensory stimuli in eukaryotes. Although dissimilar in sequence and domain organization, all known TRP channels act as polymodal cellular sensors and form tetrameric assemblies similar to those of their distant relatives, the voltage-gated potassium (Kv) channels. Here, we investigated the related questions of whether the allosteric mechanism underlying polymodal gating is common to all TRP channels, and how this mechanism differs from that underpinning Kv channel voltage sensitivity. To provide insight into these questions, we performed comparative sequence analysis on large, comprehensive ensembles of TRP and Kv channel sequences, contextualizing the patterns of conservation and correlation observed in the TRP channel sequences in light of the well-studied Kv channels. We report sequence features that are specific to TRP channels and, based on insight from recent TRPV1 structures, we suggest a model of TRP channel gating that differs substantially from the one mediating voltage sensitivity in Kv channels. The common mechanism underlying polymodal gating involves the displacement of a defect in the H-bond network of S6 that changes the orientation of the pore-lining residues at the hydrophobic gate.

| S-EPMC4485022 | biostudies-literature

Organellar TRP channels.

Project description:Mammalian transient receptor potential (TRP) channels mediate Ca2+ flux and voltage changes across membranes in response to environmental and cellular signals. At the plasma membrane, sensory TRPs act as neuronal detectors of physical and chemical environmental signals, and receptor-operated (metabotropic) TRPs decode extracellular neuroendocrine cues to control body homeostasis. In intracellular membranes, such as those in lysosomes, organellar TRPs respond to compartment-derived signals to control membrane trafficking, signal transduction, and organelle function. Complementing mouse and human genetics and high-resolution structural approaches, physiological studies employing natural agonists and synthetic inhibitors have become critical in resolving the in vivo functions of metabotropic, sensory, and organellar TRPs.

| S-EPMC6785982 | biostudies-literature

TRP Channels as Molecular Targets to Relieve Endocrine-Related Diseases.

Project description:Transient receptor potential (TRP) channels are polymodal channels capable of sensing environmental stimuli, which are widely expressed on the plasma membrane of cells and play an essential role in the physiological or pathological processes of cells as sensors. TRPs often form functional homo- or heterotetramers that act as cation channels to flow Na+ and Ca2+, change membrane potential and [Ca2+]i (cytosolic [Ca2+]), and change protein expression levels, channel attributes, and regulatory factors. Under normal circumstances, various TRP channels respond to intracellular and extracellular stimuli such as temperature, pH, osmotic pressure, chemicals, cytokines, and cell damage and depletion of Ca2+ reserves. As cation transport channels and physical and chemical stimulation receptors, TRPs play an important role in regulating secretion, interfering with cell proliferation, and affecting neural activity in these glands and their adenocarcinoma cells. Many studies have proved that TRPs are widely distributed in the pancreas, adrenal gland, and other glands. This article reviews the specific regulatory mechanisms of various TRP channels in some common glands (pancreas, salivary gland, lacrimal gland, adrenal gland, mammary gland, gallbladder, and sweat gland).

| S-EPMC9095829 | biostudies-literature

TRP channels in schistosomes.

Project description:Praziquantel (PZQ) is effectively the only drug currently available for treatment and control of schistosomiasis, a disease affecting hundreds of millions of people worldwide. Many anthelmintics, likely including PZQ, target ion channels, membrane protein complexes essential for normal functioning of the neuromusculature and other tissues. Despite this fact, only a few classes of parasitic helminth ion channels have been assessed for their pharmacological properties or for their roles in parasite physiology. One such overlooked group of ion channels is the transient receptor potential (TRP) channel superfamily. TRP channels share a common core structure, but are widely diverse in their activation mechanisms and ion selectivity. They are critical to transducing sensory signals, responding to a wide range of external stimuli. They are also involved in other functions, such as regulating intracellular calcium and organellar ion homeostasis and trafficking. Here, we review current literature on parasitic helminth TRP channels, focusing on those in schistosomes. We discuss the likely roles of these channels in sensory and locomotor activity, including the possible significance of a class of TRP channels (TRPV) that is absent in schistosomes. We also focus on evidence indicating that at least one schistosome TRP channel (SmTRPA) has atypical, TRPV1-like pharmacological sensitivities that could potentially be exploited for future therapeutic targeting.

| S-EPMC5196486 | biostudies-literature

TRP channels and analgesia.

Project description:Since cloning and characterizing the first nociceptive ion channel Transient Receptor Potential (TRP) Vanilloid 1 (TRPV1), other TRP channels involved in nociception have been cloned and characterized, which include TRP Vanilloid 2 (TRPV2), TRP Vanilloid 3 (TRPV3), TRP Vanilloid 4 (TRPV4), TRP Ankyrin 1 (TRPA1) and TRP Melastatin 8 (TRPM8), more recently TRP Canonical 1, 5, 6 (TRPC1, 5, 6), TRP Melastatin 2 (TRPM2) and TRP Melastatin 3 (TRPM3). These channels are predominantly expressed in C and Aδ nociceptors and transmit noxious thermal, mechanical and chemical sensitivities. TRP channels are modulated by pro-inflammatory mediators, neuropeptides and cytokines. Significant advances have been made targeting these receptors either by antagonists or agonists to treat painful conditions. In this review, we will discuss TRP channels as targets for next generation analgesics and the side effects that may ensue as a result of blocking/activating these receptors, because they are also involved in physiological functions such as release of vasoactive neuropeptides and regulation of vascular tone, maintenance of the body temperature, gastrointestinal motility, urinary bladder control, etc.

| S-EPMC4955588 | biostudies-literature

Molecular basis for the sensitivity of TRP channels to polyunsaturated fatty acids.

Project description: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. The primary aim was to uncover the molecular basis of PUFA sensitivity of Drosophila TRP-like (TRPL) and TRPgamma channels. Amino acid (aa) sequence alignment of the three Drosophila TRPC channels revealed 50 aa residues highly conserved in PUFA-sensitive TRPL and TRPgamma channels but not in the PUFA-insensitive TRP channel. Substitution of respective aa in TRPL by corresponding aa of TRP identified 18 residues that are necessary for PUFA-mediated activation of TRPL. Most aa positions are located within a stretch comprising transmembrane domains S2-S4, whereas six aa positions have been assigned to the proximal cytosolic C-terminus. Interestingly, residues I465 and S471 are required for activation by 5,8,11,14-eicosatetraynoic acid (ETYA) but not 5,8,11-eicosatriynoic acid (ETI). As proof of concept, we generated a PUFA-sensitive TRP channel by exchanging the corresponding aa from TRPL to TRP. Our study demonstrates a specific aa pattern in the transmembrane domains S2-S4 and the proximal C-terminus essential for TRP channel activation by PUFAs.

| S-EPMC6061713 | biostudies-literature

Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.

Project description:Transient receptor potential (TRP) channels are a large and diverse family of transmembrane ion channels that are widely expressed, have important physiological roles, and are associated with many human diseases. These proteins are actively pursued as promising drug targets, benefitting greatly from advances in structural and mechanistic studies of TRP channels. At the same time, the complex, polymodal activation and regulation of TRP channels have presented formidable challenges. In this short review, we summarize recent progresses toward understanding the structural basis of TRP channel function, as well as potential ligand binding sites that could be targeted for therapeutics. A particular focus is on the current understanding of the molecular mechanisms of TRP channel activation and regulation, where many fundamental questions remain unanswered. We believe that a deeper understanding of the functional mechanisms of TRP channels will be critical and likely transformative toward developing successful therapeutic strategies targeting these exciting proteins. This endeavor will require concerted efforts from computation, structural biology, medicinal chemistry, electrophysiology, pharmacology, drug safety and clinical studies.

| S-EPMC10808746 | biostudies-literature

Structural biology of TRP channels.

Project description:Structural studies on TRP channels, while limited, are poised for a quickened pace and rapid expansion. As of yet, no high-resolution structure of a full length TRP channel exists, but low-resolution electron cryomicroscopy structures have been obtained for 4 TRP channels, and high-resolution NMR and X-ray crystal structures have been obtained for the cytoplasmic domains, including an atypical protein kinase domain, ankyrin repeats, coiled coil domains and a Ca(2+)-binding domain, of 6 TRP channels. These structures enhance our understanding of TRP channel assembly and regulation. Continued technical advances in structural approaches promise a bright outlook for TRP channel structural biology.

| S-EPMC4356010 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data