Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor
Autor: | Eric N. Senning, Anastasiia Stratiievska, Stephen E. P. Smith, Sharona E. Gordon, Sara Nelson, Jonathan D. Lautz |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
QH301-705.5 Structural Biology and Molecular Biophysics Science Allosteric regulation TRPV1 TRPV Cation Channels Hybrid Cells Phosphatidylinositols TRPV PI3K General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Mice PIP3 Biochemistry and Chemical Biology Nerve Growth Factor None Animals Biology (General) PI3K/AKT/mTOR pathway NGF Phosphoinositide 3-kinase General Immunology and Microbiology biology Chemistry General Neuroscience Cell Membrane Long-term potentiation General Medicine Cell biology Rats Enzyme Activation TRPV2 030104 developmental biology Nerve growth factor Microscopy Fluorescence nervous system inflammation biology.protein Medicine Ankyrin repeat Phosphatidylinositol 3-Kinase Protein Binding Research Article |
Zdroj: | eLife, Vol 7 (2018) eLife |
Popis: | 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. |
Databáze: | OpenAIRE |
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