Sensing of lysophospholipids by TRPC5 calcium channel

Philippa K Flemming, Alexandra M Dedman, Shang-Zhong Xu, Jing Li, Fanning Zeng, Jacqueline Naylor, Christopher D Benham, Alan N Bateson, Katsuhiko Muraki, David J Beech

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    102 Citations (Scopus)


    TRPC calcium channels are emerging as a ubiquitous feature of vertebrate cells, but understanding of them is hampered by limited knowledge of the mechanisms of activation and identity of endogenous regulators. We have revealed that one of the TRPC channels, TRPC5, is strongly activated by common endogenous lysophospholipids including lysophosphatidylcholine (LPC) but, by contrast, not arachidonic acid. Although TRPC5 was stimulated by agonists at G-protein-coupled receptors, TRPC5 activation by LPC occurred downstream and independently of G-protein signaling. The effect was not due to the generation of reactive oxygen species or because of a detergent effect of LPC. LPC activated TRPC5 when applied to excised membrane patches and thus has a relatively direct action on the channel structure, either because of a phospholipid binding site on the channel or because of sensitivity of the channel to perturbation of the bilayer by certain lipids. Activation showed dependence on side-chain length and the chemical head-group. The data revealed a previously unrecognized lysophospholipid-sensing capability of TRPC5 that confers the property of a lipid ionotropic receptor.
    Original languageEnglish
    Pages (from-to)4977-82
    Number of pages6
    JournalJournal of Biological Chemistry
    Issue number8
    Publication statusPublished - 2006


    • Animals
    • Binding Sites
    • Calcium
    • Cell Line
    • Cell Membrane
    • Collagenases
    • DNA, Complementary
    • Detergents
    • Electrophysiology
    • GTP-Binding Proteins
    • Humans
    • Ions
    • Lipids
    • Lysophospholipids
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Oxygen
    • Patch-Clamp Techniques
    • Phospholipids
    • Protein Binding
    • Protein Isoforms
    • Reactive Oxygen Species
    • Signal Transduction
    • TRPC Cation Channels
    • Time Factors


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