scholarly journals TRP channels in health and disease at a glance

2021 ◽  
Vol 134 (13) ◽  
Author(s):  
Lixia Yue ◽  
Haoxing Xu
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Wide Spectrum ◽  
Receptor Potential ◽  
Structural Basis ◽  
Environmental Stimuli ◽  
Activation Mechanisms ◽  
Human Disorders ◽  
History Of ◽  
Transient Receptor

ABSTRACT The transient receptor potential (TRP) channel superfamily consists of a large group of non-selective cation channels that serve as cellular sensors for a wide spectrum of physical and environmental stimuli. The 28 mammalian TRPs, categorized into six subfamilies, including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin) and TRPP (polycystin), are widely expressed in different cells and tissues. TRPs exhibit a variety of unique features that not only distinguish them from other superfamilies of ion channels, but also confer diverse physiological functions. Located at the plasma membrane or in the membranes of intracellular organelles, TRPs are the cellular safeguards that sense various cell stresses and environmental stimuli and translate this information into responses at the organismal level. Loss- or gain-of-function mutations of TRPs cause inherited diseases and pathologies in different physiological systems, whereas up- or down-regulation of TRPs is associated with acquired human disorders. In this Cell Science at a Glance article and the accompanying poster, we briefly summarize the history of the discovery of TRPs, their unique features, recent advances in the understanding of TRP activation mechanisms, the structural basis of TRP Ca2+ selectivity and ligand binding, as well as potential roles in mammalian physiology and pathology.

scholarly journals Recent Advances in Lipopolysaccharide Recognition Systems

2020 ◽  
Vol 21 (2) ◽  
pp. 379 ◽  
Author(s):  
Lalita Mazgaeen ◽  
Prajwal Gurung
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Toll Like Receptor ◽  
Extracellular Milieu ◽  
Molecular Pattern ◽  
History Of ◽  
Membrane Bound ◽  
Recognition Systems ◽  
Transient Receptor

Lipopolysaccharide (LPS), commonly known as endotoxin, is ubiquitous and the most-studied pathogen-associated molecular pattern. A component of Gram-negative bacteria, extracellular LPS is sensed by our immune system via the toll-like receptor (TLR)-4. Given that TLR4 is membrane bound, it recognizes LPS in the extracellular milieu or within endosomes. Whether additional sensors, if any, play a role in LPS recognition within the cytoplasm remained unknown until recently. The last decade has seen an unprecedented unfolding of TLR4-independent LPS sensing pathways. First, transient receptor potential (TRP) channels have been identified as non-TLR membrane-bound sensors of LPS and, second, caspase-4/5 (and caspase-11 in mice) have been established as the cytoplasmic sensors for LPS. Here in this review, we detail the brief history of LPS discovery, followed by the discovery of TLR4, TRP as the membrane-bound sensor, and our current understanding of caspase-4/5/11 as cytoplasmic sensors.

Thermodynamic and structural basis of temperature-dependent gating in TRP channels

2021 ◽  
Author(s):  
Ignacio Diaz-Franulic ◽  
Christian Verdugo ◽  
Felipe Gonzalez ◽  
Fernando Gonzalez-Nilo ◽  
Ramon Latorre
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Structural Data ◽  
Structural Basis ◽  
Functional Studies ◽  
Structural Framework ◽  
Transient Receptor ◽  
Living Organisms ◽  
Open Question

Living organisms require detecting the environmental thermal clues for survival, allowing them to avoid noxious stimuli or find prey moving in the dark. In mammals, the Transient Receptor Potential ion channels superfamily is constituted by 27 polymodal receptors whose activity is controlled by small ligands, peptide toxins, protons and voltage. The thermoTRP channels subgroup exhibits unparalleled temperature dependence -behaving as heat and cold sensors. Functional studies have dissected their biophysical features in detail, and the advances of single-particle Cryogenic Electron microscopy provided the structural framework required to propose detailed channel gating mechanisms. However, merging structural and functional evidence for temperature-driven gating of thermoTRP channels has been a hard nut to crack, remaining an open question nowadays. Here we revisit the highlights on the study of heat and cold sensing in thermoTRP channels in the light of the structural data that has emerged during recent years.

scholarly journals Structural mechanisms of transient receptor potential ion channels

2020 ◽  
Vol 152 (3) ◽  
Author(s):  
Erhu Cao
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Wide Range ◽  
Human Disorders ◽  
Transient Receptor ◽  
Voltage Gated Ion Channels ◽  
Structural Mechanisms ◽  
Physical And Chemical

Transient receptor potential (TRP) ion channels are evolutionarily ancient sensory proteins that detect and integrate a wide range of physical and chemical stimuli. TRP channels are fundamental for numerous biological processes and are therefore associated with a multitude of inherited and acquired human disorders. In contrast to many other major ion channel families, high-resolution structures of TRP channels were not available before 2013. Remarkably, however, the subsequent “resolution revolution” in cryo-EM has led to an explosion of TRP structures in the last few years. These structures have confirmed that TRP channels assemble as tetramers and resemble voltage-gated ion channels in their overall architecture. But beyond the relatively conserved transmembrane core embedded within the lipid bilayer, each TRP subtype appears to be endowed with a unique set of soluble domains that may confer diverse regulatory mechanisms. Importantly, TRP channel TR structures have revealed sites and mechanisms of action of numerous synthetic and natural compounds, as well as those for endogenous ligands such as lipids, Ca2+, and calmodulin. Here, I discuss these recent findings with a particular focus on the conserved transmembrane region and how these structures may help to rationally target this important class of ion channels for the treatment of numerous human conditions.

scholarly journals Transient receptor potential channels: current perspectives on evolution, structure, function and nomenclature

2020 ◽  
Vol 287 (1933) ◽  
pp. 20201309
Author(s):  
Nathaniel J. Himmel ◽  
Daniel N. Cox
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Phylogenetic Analyses ◽  
Receptor Potential ◽  
Original Description ◽  
Transient Receptor Potential Channels ◽  
Wide Range ◽  
History Of ◽  
Potential Channels ◽  
Transient Receptor

The transient receptor potential superfamily of ion channels (TRP channels) is widely recognized for the roles its members play in sensory nervous systems. However, the incredible diversity within the TRP superfamily, and the wide range of sensory capacities found therein, has also allowed TRP channels to function beyond sensing an organism's external environment, and TRP channels have thus become broadly critical to (at least) animal life. TRP channels were originally discovered in Drosophila and have since been broadly studied in animals; however, thanks to a boom in genomic and transcriptomic data, we now know that TRP channels are present in the genomes of a variety of creatures, including green algae, fungi, choanoflagellates and a number of other eukaryotes. As a result, the organization of the TRP superfamily has changed radically from its original description. Moreover, modern comprehensive phylogenetic analyses have brought to light the vertebrate-centricity of much of the TRP literature; much of the nomenclature has been grounded in vertebrate TRP subfamilies, resulting in a glossing over of TRP channels in other taxa. Here, we provide a comprehensive review of the function, structure and evolutionary history of TRP channels, and put forth a more complete set of non-vertebrate-centric TRP family, subfamily and other subgroup nomenclature.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

2011 ◽  
Vol 110 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Kaori Ono ◽  
Masako Tsukamoto-Yasui ◽  
Yoshiko Hara-Kimura ◽  
Naohiko Inoue ◽  
Yoshihito Nogusa ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Low Frequency ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Intragastric Administration ◽  
Brown Adipose ◽  
Reflex Arc ◽  
Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

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