Regulation of the cold-sensing TRPM8 channels by phosphoinositides and Gq-coupled receptors. 2020

Luyu Liu, and Tibor Rohacs
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, USA.

The Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is an important sensor of environmental cold temperatures. Cold- and menthol-induced activation of this channel requires the presence of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. This review discusses recent findings on the role of PI(4,5)P2 and G-proteins in the modulation of TRPM8 upon receptor activation. We will also summarize knowledge on the role of PI(4,5)P2 in Ca2+ dependent desensitization/adaptation of TRPM8 activity, and recent advances in the structural basis of how this lipid binds to TRPM8.

UI MeSH Term Description Entries
D010716 Phosphatidylinositols Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids. Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
D003080 Cold Temperature An absence of warmth or heat or a temperature notably below an accustomed norm. Cold,Cold Temperatures,Temperature, Cold,Temperatures, Cold
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D050051 Transient Receptor Potential Channels A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN REPEATS are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES. TRP Cation Channel,Transient Receptor Potential Cation Channel,Transient Receptor Potential Channel,TRP Cation Channels,TRP Membrane Proteins,Transient Receptor Potential Cation Channels,Cation Channel, TRP,Cation Channels, TRP,Channel, TRP Cation,Channels, TRP Cation,Membrane Proteins, TRP,Proteins, TRP Membrane
D050053 TRPM Cation Channels A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes. TRPM Cation Channel,Transient Receptor Potential Channels, Type M,Cation Channel, TRPM,Cation Channels, TRPM,Channel, TRPM Cation,Channels, TRPM Cation
D019269 Phosphatidylinositol 4,5-Diphosphate A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994) PtdInsP2,Phosphatidylinositol 4,5-Biphosphate,Phosphatidylinositol Phosphate, PtdIns(4,5)P2,Phosphatidylinositol-4,5-Biphosphate,PtIns 4,5-P2,PtdIns(4,5)P2,PtdInsP,4,5-Biphosphate, Phosphatidylinositol,4,5-Diphosphate, Phosphatidylinositol,Phosphatidylinositol 4,5 Biphosphate,Phosphatidylinositol 4,5 Diphosphate

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