PT  - JOURNAL ARTICLE
AU  - Prescott, Elizabeth D.
AU  - Julius, David
TI  - A Modular PIP<sub>2</sub> Binding Site as a Determinant of Capsaicin Receptor Sensitivity
AID  - 10.1126/science.1083646
DP  - 2003 May 23
TA  - Science
PG  - 1284--1288
VI  - 300
IP  - 5623
4099  - http://science.sciencemag.org/content/300/5623/1284.short
4100  - http://science.sciencemag.org/content/300/5623/1284.full
SO  - Science2003 May 23; 300
AB  - 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.