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

eLife

Sharona E Gordon¹  Jonathan D Lautz²  Stephen EP Smith²  Sara Nelson³  Eric N Senning³  Anastasiia Stratiievska³ 

[1] Department of Pediatrics and Graduate Program in Neuroscience, University of Washington, Seattle, United States;Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States;Department of Physiology and Biophysics, University of Washington, Seattle, United States;

关键词: TRPV1;    NGF;    PI3K;    inflammation;    PIP3;    TRPV2;   

DOI  :  10.7554/eLife.38869

来源: DOAJ

【 摘 要 】

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 regulation was involved. Further, other TRPV channels with conserved ARDs also potentiated NGF-induced PI3K activity. Our data demonstrate a novel reciprocal regulation of PI3K signaling by the ARD of TRPV channels.

【 授权许可】

Unknown