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- Title
A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity.
- Authors
Prescott, Elizabeth D; Julius, David
- Abstract
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.
- Publication
Science (New York, N.Y.), 2003, Vol 300, Issue 5623, p1284
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1083646