AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

Sraboni Chaudhury, Manjot Bal, Sergei Belugin, Mark S. Shapiro, Nathaniel A. Jeske

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1.Results: In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity.Conclusions: the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.

Original languageEnglish (US)
Article number34
JournalMolecular Pain
Volume7
DOIs
StatePublished - May 14 2011

Fingerprint

TRPV Cation Channels
Calmodulin
Protein Kinases
Calcium
Cricetulus
Ovary
Phosphorylation
Fluorescence Resonance Energy Transfer
Nociceptors
Molecular Models
Electrophysiology
Sensory Receptor Cells
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Fluorescence
Binding Sites
Neurons

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

Chaudhury, S., Bal, M., Belugin, S., Shapiro, M. S., & Jeske, N. A. (2011). AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin. Molecular Pain, 7, [34]. https://doi.org/10.1186/1744-8069-7-34

AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin. / Chaudhury, Sraboni; Bal, Manjot; Belugin, Sergei; Shapiro, Mark S.; Jeske, Nathaniel A.

In: Molecular Pain, Vol. 7, 34, 14.05.2011.

Research output: Contribution to journalArticle

Chaudhury, S, Bal, M, Belugin, S, Shapiro, MS & Jeske, NA 2011, 'AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin', Molecular Pain, vol. 7, 34. https://doi.org/10.1186/1744-8069-7-34
Chaudhury, Sraboni ; Bal, Manjot ; Belugin, Sergei ; Shapiro, Mark S. ; Jeske, Nathaniel A. / AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin. In: Molecular Pain. 2011 ; Vol. 7.
@article{6fc52d3ef743430cb706a1d76269fa8f,
title = "AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin",
abstract = "Background: The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1.Results: In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity.Conclusions: the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.",
author = "Sraboni Chaudhury and Manjot Bal and Sergei Belugin and Shapiro, {Mark S.} and Jeske, {Nathaniel A.}",
year = "2011",
month = "5",
day = "14",
doi = "10.1186/1744-8069-7-34",
language = "English (US)",
volume = "7",
journal = "Molecular Pain",
issn = "1744-8069",
publisher = "BioMed Central",

}

TY - JOUR

T1 - AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

AU - Chaudhury, Sraboni

AU - Bal, Manjot

AU - Belugin, Sergei

AU - Shapiro, Mark S.

AU - Jeske, Nathaniel A.

PY - 2011/5/14

Y1 - 2011/5/14

N2 - Background: The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1.Results: In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity.Conclusions: the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.

AB - Background: The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1.Results: In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity.Conclusions: the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.

UR - http://www.scopus.com/inward/record.url?scp=79955821040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955821040&partnerID=8YFLogxK

U2 - 10.1186/1744-8069-7-34

DO - 10.1186/1744-8069-7-34

M3 - Article

C2 - 21569553

AN - SCOPUS:79955821040

VL - 7

JO - Molecular Pain

JF - Molecular Pain

SN - 1744-8069

M1 - 34

ER -