Research article summary (published 30 Apr 2008):

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

Full 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.

Author information

Author/s: Kim, Andrew Y (AY); Tang, Zongxiang (Z); Liu, Qin (Q); Patel, Kush N (KN); Maag, David (D); Geng, Yixun (Y); Dong, Xinzhong (X);

Affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.

Grants: NS054791 (Agency:NINDS NIH HHS) ; R01 NS054791-01A1 (Agency:NINDS NIH HHS) ; R01 NS054791-02 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Cell (Cell), published in United States. (Language: eng)

Reference: 2008-May; vol 133 (issue 3) : pp 475-85

Dates: Created 2008/05/05; Completed 2008/05/21; Revised 2009/05/05;

PMID: 18455988, status: MEDLINE (last retrieved date: 5/6/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Amino Acid Sequence Animals Capsaicin - metabolism Carrier Proteins - chemistry; genetics; metabolism Ganglia, Spinal - metabolism Hot Temperature Membrane Proteins - chemistry; genetics; metabolism Mice

Mice Mice, Knockout Molecular Sequence Data Neurons, Afferent - metabolism Nociceptors - metabolism Phosphatidylinositol 4,5-Diphosphate - metabolism Sequence Alignment TRPV Cation Channels - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Carrier Proteins (0) ; Membrane Proteins (0) ; Phosphatidylinositol 4,5-Diphosphate (0) ; Pirt protein, mouse (0) ; TRPV Cation Channels (0) ; TRPV1 protein, mouse (0) ; Capsaicin (404-86-4)

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