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bioRxiv · 10.1101/346718

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

Stratiievska, A.·Nelson, S.·Senning, E. N.·Lautz, J. D.·Smith, S. E. P.·Gordon, S. E.
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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 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 2-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 whereas TRP channels lacking ARDs did not. Our data demonstrate a novel reciprocal regulation of PI3K signaling by the ARD of TRPV channels.

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Stratiievska, A., Nelson, S., Senning, E. N., Lautz, J. D., Smith, S. E. P., Gordon, S. E.. 2018-06-13. Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor. https://doi.org/10.1101/346718

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