Publication Date:
2003-05-24
Description:
The capsaicin receptor (TRPV1), a heat-activated ion channel of the pain pathway, is sensitized by phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis after phospholipase C activation. We identify a site within the C-terminal domain of TRPV1 that is required for PIP2-mediated inhibition of channel gating. Mutations that weaken PIP2-TRPV1 interaction reduce thresholds for chemical or thermal stimuli, whereas TRPV1 channels in which this region is replaced with a lipid-binding domain from PIP2-activated potassium channels remain inhibited by PIP2. The PIP2-interaction domain therefore serves as a critical determinant of thermal threshold and dynamic sensitivity range, tuning TRPV1, and thus the sensory neuron, to appropriately detect heat under normal or pathophysiological conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prescott, Elizabeth D -- Julius, David -- New York, N.Y. -- Science. 2003 May 23;300(5623):1284-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-2140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12764195" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Arsenicals/pharmacology
;
Binding Sites
;
Capsaicin/metabolism/pharmacology
;
Carrier Proteins
;
Hot Temperature
;
Humans
;
Ion Channel Gating
;
Membrane Proteins
;
Molecular Sequence Data
;
Mutation
;
Oocytes
;
Patch-Clamp Techniques
;
Phosphatidylinositol 4,5-Diphosphate/*metabolism
;
Phosphorylation
;
Potassium Channels, Inwardly Rectifying/chemistry/genetics/metabolism
;
Protein Structure, Tertiary
;
Rats
;
Receptor, Epidermal Growth Factor/metabolism
;
Receptor, trkA/metabolism
;
Receptors, Drug/*chemistry/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Sequence Deletion
;
Type C Phospholipases/metabolism
;
Xenopus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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