Lysophosphatidic Acid Directly Activates TRPV1 Through a C-terminal Binding Site

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2011 Nov 22

PMID 22101604

Citations 116

Authors

Andres Nieto-Posadas

Giovanni Picazo-Juarez

Itzel Llorente

Andres Jara-Oseguera

Sara Morales-Lazaro

Diana Escalante-Alcalde

Leon D Islas

Tamara Rosenbaum

Affiliations

Soon will be listed here.

Abstract

Since 1992, there has been growing evidence that the bioactive phospholipid lysophosphatidic acid (LPA), whose amounts are increased upon tissue injury, activates primary nociceptors resulting in neuropathic pain. The TRPV1 ion channel is expressed in primary afferent nociceptors and is activated by physical and chemical stimuli. Here we show that in control mice LPA produces acute pain-like behaviors, which are substantially reduced in Trpv1-null animals. Our data also demonstrate that LPA activates TRPV1 through a unique mechanism that is independent of G protein-coupled receptors, contrary to what has been widely shown for other ion channels, by directly interacting with the C terminus of the channel. We conclude that TRPV1 is a direct molecular target of the pain-producing molecule LPA and that this constitutes, to our knowledge, the first example of LPA binding directly to an ion channel to acutely regulate its function.

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