Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the Ca2+/calmodulin-dependent PP2B (protein phosphatase 2B, also known as calcineurin) towards membrane-associated substrates. Recent evidence indicates that AKAP150-anchored PKA and PKC phosphorylate and sensitize the TRPV1 (transient receptor potential subfamily V type 1 channel, also known as the capsaicin receptor). In the present study, we explore the hypothesis that an AKAP150-associated pool of PP2B catalyses the dephosphorylation and desensitization of TRPV1. Biochemical, electrophysiological and cell-based experiments indicate that PP2B associates with AKAP150 and TRPV1 in cultured TG (trigeminal ganglia) neurons. Gene silencing of AKAP150 reduces basal phosphorylation of TRPV1. However, functional studies in neurons isolated from AKAP150−/− mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1. Behavioural analysis of AKAP150−/− mice further support this notion, demonstrating that agonist-stimulated desensitization of TRPV1 is sensitive to PP2B inhibition and does not rely on AKAP150. These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components.
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December 2010
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Research Article|
November 25 2010
PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150
Elaine D. Por;
Elaine D. Por
*Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, U.S.A.
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Bret K. Samelson;
Bret K. Samelson
†Howard Hughes Medical Institute, Department of Pharmacology, Box 357750, University of Washington School of Medicine, Seattle, WA 98195-7280, U.S.A.
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Sergei Belugin;
Sergei Belugin
‡Department of Endodontics, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, U.S.A.
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Armen N. Akopian;
Armen N. Akopian
‡Department of Endodontics, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, U.S.A.
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John D. Scott;
John D. Scott
†Howard Hughes Medical Institute, Department of Pharmacology, Box 357750, University of Washington School of Medicine, Seattle, WA 98195-7280, U.S.A.
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Nathaniel A. Jeske
Nathaniel A. Jeske
1
*Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, U.S.A.
§Department of Oral and Maxillofacial Surgery, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, U.S.A.
1To whom correspondence should be addressed (email Jeske@uthscsa.edu).
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Publisher: Portland Press Ltd
Received:
June 24 2010
Revision Received:
September 22 2010
Accepted:
September 30 2010
Accepted Manuscript online:
September 30 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 432 (3): 549–556.
Article history
Received:
June 24 2010
Revision Received:
September 22 2010
Accepted:
September 30 2010
Accepted Manuscript online:
September 30 2010
Citation
Elaine D. Por, Bret K. Samelson, Sergei Belugin, Armen N. Akopian, John D. Scott, Nathaniel A. Jeske; PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150. Biochem J 15 December 2010; 432 (3): 549–556. doi: https://doi.org/10.1042/BJ20100936
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