Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor
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 t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/38869 |
| _version_ | 1818028265566109696 |
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| author | Anastasiia Stratiievska Sara Nelson Eric N Senning Jonathan D Lautz Stephen EP Smith Sharona E Gordon |
| author_facet | Anastasiia Stratiievska Sara Nelson Eric N Senning Jonathan D Lautz Stephen EP Smith Sharona E Gordon |
| author_sort | Anastasiia Stratiievska |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:01:03Z |
| format | Article |
| id | doaj.art-ab8c129dbac1436fa79ca6982fce5e6b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:01:03Z |
| publishDate | 2018-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ab8c129dbac1436fa79ca6982fce5e6b2022-12-22T02:01:23ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.38869Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factorAnastasiia Stratiievska0https://orcid.org/0000-0002-5523-0773Sara Nelson1Eric N Senning2Jonathan D Lautz3Stephen EP Smith4Sharona E Gordon5https://orcid.org/0000-0002-0914-3361Department of Physiology and Biophysics, University of Washington, Seattle, United StatesDepartment of Physiology and Biophysics, University of Washington, Seattle, United StatesDepartment of Physiology and Biophysics, University of Washington, Seattle, United StatesCenter for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United StatesCenter for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States; Department of Pediatrics and Graduate Program in Neuroscience, University of Washington, Seattle, United StatesDepartment of Physiology and Biophysics, University of Washington, Seattle, United StatesAlthough 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.https://elifesciences.org/articles/38869TRPV1NGFPI3KinflammationPIP3TRPV2 |
| spellingShingle | Anastasiia Stratiievska Sara Nelson Eric N Senning Jonathan D Lautz Stephen EP Smith Sharona E Gordon Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor eLife TRPV1 NGF PI3K inflammation PIP3 TRPV2 |
| title | Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor |
| title_full | Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor |
| title_fullStr | Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor |
| title_full_unstemmed | Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor |
| title_short | Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor |
| title_sort | reciprocal regulation among trpv1 channels and phosphoinositide 3 kinase in response to nerve growth factor |
| topic | TRPV1 NGF PI3K inflammation PIP3 TRPV2 |
| url | https://elifesciences.org/articles/38869 |
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