title: A-kinase anchoring protein 150 mediates transient receptor potential family V type 1 sensitivity to phosphatidylinositol-4,5-bisphosphate.
abstract: 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 (PIP(2)) 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 PIP(2) on TRPV1 are mediated through AKAP150. In trigeminal neurons and CHO cells, the manipulation of cellular PIP(2) led to significant changes in the association of AKAP150 and TRPV1. Following PIP(2) 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 PIP(2)-mediated inhibition of TRPV1 in the whole-cell environment requires expression of the scaffolding protein. Furthermore, the addition of PIP(2) to neurons isolated from AKAP150 wild-type mice reduced PKA sensitization of TRPV1 compared with isolated neurons from AKAP150(-/-) mice. These findings suggest that PIP(2) degradation increases AKAP150 association with TRPV1 in the whole-cell environment, leading to sensitization of the receptor to nociceptive stimuli.
authors.affiliation: Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center, San Antonio, Texas 78229, USA. jeske@UTHSCSA.edu
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Jeske
authors.forename: Elaine D
authors.initials: ED
authors.lastname: Por
authors.forename: Sergei
authors.initials: S
authors.lastname: Belugin
authors.forename: Sraboni
authors.initials: S
authors.lastname: Chaudhury
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Berg
authors.forename: Armen N
authors.initials: AN
authors.lastname: Akopian
authors.forename: Michael A
authors.initials: MA
authors.lastname: Henry
authors.forename: Ruben
authors.initials: R
authors.lastname: Gomez
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D050916:TRPV Cation Channels / Q000378:metabolism*; D046509:Tissue Culture Techniques; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C520665:Akap5 protein, mouse; D019269:Phosphatidylinositol 4,5-Diphosphate; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D002118:Calcium