Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor.

ABSTRACT: Although it has been known for over a decade that the inflammatory mediator NGF sensitizes pain-receptor neurons through increased trafficking of TRPV1 channels to the plasma membrane, the mechanism by which this occurs remains mysterious. NGF activates phosphoinositide 3-kinase (PI3K), the enzyme that generates PI(3,4)P₂ and PIP₃, and PI3K activity is required for sensitization. One tantalizing hint came from the finding that the N-terminal region of TRPV1 interacts directly with PI3K. Using two-color total internal reflection fluorescence microscopy, we show that TRPV1 potentiates NGF-induced PI3K activity. A soluble TRPV1 fragment corresponding to the N-terminal Ankyrin repeats domain (ARD) was sufficient to produce this potentiation, indicating that allosteric reg

SUBMITTER: Stratiievska A 

PROVIDER: S-EPMC6312403 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature