Journal club 2013-07-12

Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site

Andrés Nieto-Posadas1, Giovanni Picazo-Juárez1, Itzel Llorente1, Andrés Jara-Oseguera2,
Sara Morales-Lázaro1, Diana Escalante-Alcalde1*, León D Islas2* & Tamara Rosenbaum1*

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.

nchembio.712