Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol

Thomas Hofmann, Alexander G. Obukhov, Michael Schaefer, Christian Harteneck, Thomas Gudermann, Günter Schultz

Research output: Contribution to journalArticle

1121 Citations (Scopus)

Abstract

Eukaryotic cells respond to many hormones and neurotransmitters with increased activity of the enzyme phospholipase C and a subsequent rise in the concentration of intracellular free calcium ([Ca2+](i)). The increase in [Ca2+](i) occurs as a result of the release of Ca2+ from intracellular stores and an influx of Ca2+ through the plasma membrane; this influx of Ca2+ may or may not be store-dependent. Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry. Here we describe the molecular mechanism of store-depletion-independent activation of a subfamily of mammalian TRPC channels. We find that hTRPC6 is a non-selective cation channel that is activated by diacylglycerol in a membrane-delimited fashion, independently of protein kinases C activated by diacylglycerol. Although hTRPC3, the closest structural relative of hTRPC6, is activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1 are unresponsive to the lipid mediator. Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol.

Original languageEnglish (US)
Pages (from-to)259-263
Number of pages5
JournalNature
Volume397
Issue number6716
DOIs
StatePublished - Jan 21 1999

Fingerprint

Diglycerides
Cations
Type C Phospholipases
Second Messenger Systems
Eukaryotic Cells
Protein Kinase C
Neurotransmitter Agents
Cell Membrane
Hormones
Calcium
Lipids
Membranes
Enzymes
TRPC3 cation channel
human TRPC6 protein
Proteins

ASJC Scopus subject areas

  • General

Cite this

Hofmann, T., Obukhov, A. G., Schaefer, M., Harteneck, C., Gudermann, T., & Schultz, G. (1999). Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature, 397(6716), 259-263. https://doi.org/10.1038/16711

Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. / Hofmann, Thomas; Obukhov, Alexander G.; Schaefer, Michael; Harteneck, Christian; Gudermann, Thomas; Schultz, Günter.

In: Nature, Vol. 397, No. 6716, 21.01.1999, p. 259-263.

Research output: Contribution to journalArticle

Hofmann, T, Obukhov, AG, Schaefer, M, Harteneck, C, Gudermann, T & Schultz, G 1999, 'Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol', Nature, vol. 397, no. 6716, pp. 259-263. https://doi.org/10.1038/16711
Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999 Jan 21;397(6716):259-263. https://doi.org/10.1038/16711
Hofmann, Thomas ; Obukhov, Alexander G. ; Schaefer, Michael ; Harteneck, Christian ; Gudermann, Thomas ; Schultz, Günter. / Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. In: Nature. 1999 ; Vol. 397, No. 6716. pp. 259-263.
@article{99f74d467e214a54826443ab938af4b5,
title = "Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol",
abstract = "Eukaryotic cells respond to many hormones and neurotransmitters with increased activity of the enzyme phospholipase C and a subsequent rise in the concentration of intracellular free calcium ([Ca2+](i)). The increase in [Ca2+](i) occurs as a result of the release of Ca2+ from intracellular stores and an influx of Ca2+ through the plasma membrane; this influx of Ca2+ may or may not be store-dependent. Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry. Here we describe the molecular mechanism of store-depletion-independent activation of a subfamily of mammalian TRPC channels. We find that hTRPC6 is a non-selective cation channel that is activated by diacylglycerol in a membrane-delimited fashion, independently of protein kinases C activated by diacylglycerol. Although hTRPC3, the closest structural relative of hTRPC6, is activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1 are unresponsive to the lipid mediator. Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol.",
author = "Thomas Hofmann and Obukhov, {Alexander G.} and Michael Schaefer and Christian Harteneck and Thomas Gudermann and G{\"u}nter Schultz",
year = "1999",
month = "1",
day = "21",
doi = "10.1038/16711",
language = "English (US)",
volume = "397",
pages = "259--263",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6716",

}

TY - JOUR

T1 - Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol

AU - Hofmann, Thomas

AU - Obukhov, Alexander G.

AU - Schaefer, Michael

AU - Harteneck, Christian

AU - Gudermann, Thomas

AU - Schultz, Günter

PY - 1999/1/21

Y1 - 1999/1/21

N2 - Eukaryotic cells respond to many hormones and neurotransmitters with increased activity of the enzyme phospholipase C and a subsequent rise in the concentration of intracellular free calcium ([Ca2+](i)). The increase in [Ca2+](i) occurs as a result of the release of Ca2+ from intracellular stores and an influx of Ca2+ through the plasma membrane; this influx of Ca2+ may or may not be store-dependent. Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry. Here we describe the molecular mechanism of store-depletion-independent activation of a subfamily of mammalian TRPC channels. We find that hTRPC6 is a non-selective cation channel that is activated by diacylglycerol in a membrane-delimited fashion, independently of protein kinases C activated by diacylglycerol. Although hTRPC3, the closest structural relative of hTRPC6, is activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1 are unresponsive to the lipid mediator. Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol.

AB - Eukaryotic cells respond to many hormones and neurotransmitters with increased activity of the enzyme phospholipase C and a subsequent rise in the concentration of intracellular free calcium ([Ca2+](i)). The increase in [Ca2+](i) occurs as a result of the release of Ca2+ from intracellular stores and an influx of Ca2+ through the plasma membrane; this influx of Ca2+ may or may not be store-dependent. Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry. Here we describe the molecular mechanism of store-depletion-independent activation of a subfamily of mammalian TRPC channels. We find that hTRPC6 is a non-selective cation channel that is activated by diacylglycerol in a membrane-delimited fashion, independently of protein kinases C activated by diacylglycerol. Although hTRPC3, the closest structural relative of hTRPC6, is activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1 are unresponsive to the lipid mediator. Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol.

UR - http://www.scopus.com/inward/record.url?scp=0033590450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033590450&partnerID=8YFLogxK

U2 - 10.1038/16711

DO - 10.1038/16711

M3 - Article

C2 - 9930701

AN - SCOPUS:0033590450

VL - 397

SP - 259

EP - 263

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6716

ER -