Pirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1

Andrew Y. Kim, Zongxiang Tang, Qin Liu, Kush N. Patel, David Maag, Yixun Geng, Xinzhong Dong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)475-485
Number of pages11
JournalCell
Volume133
Issue number3
DOIs
StatePublished - May 2 2008
Externally publishedYes

Fingerprint

Phosphatidylinositols
Carrier Proteins
Capsaicin
Hot Temperature
Spinal Ganglia
Neurons
vanilloid receptor subtype 1
Nociceptors
Membrane Proteins
Cells
Sensors

Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Pirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1. / Kim, Andrew Y.; Tang, Zongxiang; Liu, Qin; Patel, Kush N.; Maag, David; Geng, Yixun; Dong, Xinzhong.

In: Cell, Vol. 133, No. 3, 02.05.2008, p. 475-485.

Research output: Contribution to journalArticle

Kim, AY, Tang, Z, Liu, Q, Patel, KN, Maag, D, Geng, Y & Dong, X 2008, 'Pirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1', Cell, vol. 133, no. 3, pp. 475-485. https://doi.org/10.1016/j.cell.2008.02.053
Kim, Andrew Y. ; Tang, Zongxiang ; Liu, Qin ; Patel, Kush N. ; Maag, David ; Geng, Yixun ; Dong, Xinzhong. / Pirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1. In: Cell. 2008 ; Vol. 133, No. 3. pp. 475-485.
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