RT Journal Article
SR Electronic
T1 A-Kinase Anchoring Protein 150 Mediates Transient Receptor Potential Family V Type 1 Sensitivity to Phosphatidylinositol-4,5-Bisphosphate
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8681
OP 8688
DO 10.1523/JNEUROSCI.0020-11.2011
VO 31
IS 23
A1 Nathaniel A. Jeske
A1 Elaine D. Por
A1 Sergei Belugin
A1 Sraboni Chaudhury
A1 Kelly A. Berg
A1 Armen N. Akopian
A1 Michael A. Henry
A1 Ruben Gomez
YR 2011
UL http://www.jneurosci.org/content/31/23/8681.abstract
AB A-kinase anchoring protein 150 (AKAP150) is a scaffolding protein that controls protein kinase A- and C-mediated phosphorylation of the transient receptor potential family V type 1 (TRPV1), dictating receptor response to nociceptive stimuli. The phospholipid phosphatidylinositol-4,5-bisphosphate (PIP2) anchors AKAP150 to the plasma membrane in naive conditions and also affects TRPV1 activity. In the present study, we sought to determine whether the effects of PIP2 on TRPV1 are mediated through AKAP150. In trigeminal neurons and CHO cells, the manipulation of cellular PIP2 led to significant changes in the association of AKAP150 and TRPV1. Following PIP2 degradation, increased TRPV1:AKAP150 coimmunoprecipitation was observed, resulting in increased receptor response to capsaicin treatment. Phospholipase C activation in neurons isolated from AKAP150−/− animals indicated that PIP2-mediated inhibition of TRPV1 in the whole-cell environment requires expression of the scaffolding protein. Furthermore, the addition of PIP2 to neurons isolated from AKAP150 wild-type mice reduced PKA sensitization of TRPV1 compared with isolated neurons from AKAP150−/− mice. These findings suggest that PIP2 degradation increases AKAP150 association with TRPV1 in the whole-cell environment, leading to sensitization of the receptor to nociceptive stimuli.