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Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1.

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 (PIP2), and can potentiate TRPV1. The PIP2 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 PIP2 requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity.

Pubmed ID: 18455988

Authors

  • Kim AY
  • Tang Z
  • Liu Q
  • Patel KN
  • Maag D
  • Geng Y
  • Dong X

Journal

Cell

Publication Data

May 2, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS054791
  • Agency: NINDS NIH HHS, Id: R01 NS054791
  • Agency: NINDS NIH HHS, Id: R01 NS054791-01A1
  • Agency: NINDS NIH HHS, Id: R01 NS054791-02
  • Agency: NINDS NIH HHS, Id: R01 NS054791-03
  • Agency: NINDS NIH HHS, Id: R01 NS054791-04
  • Agency: NEI NIH HHS, Id: T32 EY017203

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Capsaicin
  • Carrier Proteins
  • Ganglia, Spinal
  • Hot Temperature
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Neurons, Afferent
  • Nociceptors
  • Phosphatidylinositol 4,5-Diphosphate
  • Sequence Alignment
  • TRPV Cation Channels