PMID- 22789851
OWN - NLM
STAT- MEDLINE
DCOM- 20121108
LR  - 20220408
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 424
IP  - 2
DP  - 2012 Jul 27
TI  - Activation of NMDA receptors leads to phosphorylation of TRPV1 S800 by protein 
      kinase C and A-Kinase anchoring protein 150 in rat trigeminal ganglia.
PG  - 358-63
LID - 10.1016/j.bbrc.2012.07.008 [doi]
AB  - A-Kinase anchoring protein 150 (AKAP150) is required for the phosphorylation of 
      transient receptor potential cation channel subfamily V member 1 (TRPV1) by PKA 
      or PKC in sensory neurons and, hence, affects TRPV1-dependent hyperalgesia under 
      pathological conditions. Recently, we showed that the activation of 
      N-methyl-D-aspartate (NMDA) receptors sensitizes TRPV1 by enhancing serine 
      phosphorylation through PKC in trigeminal nociceptors. In this study, we extended 
      this observation by investigating whether AKAP150 mediates NMDA-induced 
      phosphorylation of TRPV1 via PKC in native sensory neurons in the rat. By 
      adopting a phospho-specific antibody combined with a surface biotinylation assay, 
      we first assessed NMDA-induced changes in the phosphorylation level of serine 800 
      residues (S800) in TRPV1 delimited to cell surface membrane in cultured 
      trigeminal ganglia (TG). The biotinylation assay yielded that the application of 
      NMDA significantly increased the phosphorylation of S800 (p-S800) of TRPV1 at 
      time points correlating with the development of NMDA-induced mechanical 
      hyperalgesia [10]. We then obtained a siRNA sequence against AKAP150 that 
      dose-dependently down-regulated the AKAP150 protein. Pretreatment of TG culture 
      with the siRNA, but not mismatch sequences, prevented the NMDA-induced 
      phosphorylation of serine residues of total TRPV1 as well as S800 of membrane 
      bound TRPV1. We confirmed that AKAP150 co-immunoprecipitated with TRPV1 and 
      demonstrated that it also co-immunoprecipitated with NMDA receptor subunits (NR1 
      and NR2B) in TG. These data offer novel information that the activation of 
      NMDA-induced TRPV1 sensitization involves p-S800 of TRPV1 in cell surface 
      membrane in native sensory neurons and that AKAP150 is required for NMDA-and 
      PKC-mediated phosphorylation of TRPV1 S800. Therefore, we propose that the NMDA 
      receptor, AKAP150, and TRPV1 forms a signaling complex that underlies the 
      sensitization of trigeminal nociceptors by modulating phosphorylation of specific 
      TRPV1 residues.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Lee, Jongseok
AU  - Lee J
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, Program in Neuroscience, 650 W. Baltimore Street, Baltimore, MD 21201, 
      United States.
FAU - Chung, Man-Kyo
AU  - Chung MK
FAU - Ro, Jin Y
AU  - Ro JY
LA  - eng
GR  - R01 DE016062/DE/NIDCR NIH HHS/United States
GR  - R01DE16062/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120710
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (A Kinase Anchor Proteins)
RN  - 0 (Akap5 protein, rat)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Trpv1 protein, rat)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - A Kinase Anchor Proteins/genetics/*metabolism
MH  - Animals
MH  - Immunoprecipitation
MH  - Male
MH  - Nociceptors/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*agonists
MH  - Serine/metabolism
MH  - TRPV Cation Channels/*metabolism
MH  - Trigeminal Ganglion/*metabolism
PMC - PMC3408820
MID - NIHMS393081
EDAT- 2012/07/14 06:00
MHDA- 2012/11/09 06:00
PMCR- 2013/07/27
CRDT- 2012/07/14 06:00
PHST- 2012/07/02 00:00 [received]
PHST- 2012/07/03 00:00 [accepted]
PHST- 2012/07/14 06:00 [entrez]
PHST- 2012/07/14 06:00 [pubmed]
PHST- 2012/11/09 06:00 [medline]
PHST- 2013/07/27 00:00 [pmc-release]
AID - S0006-291X(12)01282-X [pii]
AID - 10.1016/j.bbrc.2012.07.008 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Jul 27;424(2):358-63. doi: 
      10.1016/j.bbrc.2012.07.008. Epub 2012 Jul 10.