Sensing of lysophospholipids by TRPC5 calcium channel.
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.
Flemming
Philippa K
PK
Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Dedman
Alexandra M
AM
Xu
Shang-Zhong
SZ
Li
Jing
J
Zeng
Fanning
F
Naylor
Jacqueline
J
Benham
Christopher D
CD
Bateson
Alan N
AN
Muraki
Katsuhiko
K
Beech
David J
DJ
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000737:chemistry; D006801:Humans; D007477:Ions; D008055:Lipids / Q000737:chemistry; D008246:Lysophospholipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000737:chemistry* / Q000502:physiology; D013997:Time Factors
D018076:DNA, Complementary; D003902:Detergents; D007477:Ions; D008055:Lipids; D008246:Lysophospholipids; D010743:Phospholipids; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D017364:Collagenases; D019204:GTP-Binding Proteins; D010100:Oxygen; D002118:Calcium