期刊
CELL
卷 133, 期 3, 页码 475-485出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.02.053
关键词
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资金
- NEI NIH HHS [T32 EY017203] Funding Source: Medline
- NINDS NIH HHS [R01 NS054791-02, R01 NS054791, R01 NS054791-04, NS054791, R01 NS054791-01A1, R37 NS054791, R01 NS054791-03] Funding Source: Medline
Transient receptor potential vanilloid 1 (TRPV1) is a molecular sensor of noxious heat and capsaicin. Its channel activity can be modulated by several mechanisms. Here we identify a membrane protein, Pirt, as a regulator of TRPV1. Pirt is expressed in most nociceptive neurons in the dorsal root ganglia (DRG) including TRPV1-positive cells. Pirt null mice show impaired responsiveness to noxious heat and capsaicin. Noxious heat- and capsaicin-sensitive currents in Pirt-deficient DRG neurons are significantly attenuated. Heterologous expression of Pirt strongly enhances TRPV1-mediated currents. Furthermore, the C terminus of Pirt binds to TRPV1 and several phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP(2)), and can potentiate TRPV1. The PIP(2) binding is dependent on the cluster of basic residues in the Pirt C terminus and is crucial for Pirt regulation of TRPV1. Importantly, the enhancement of TRPV1 by PIP(2) requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity.
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