AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin
<p>Abstract</p> <p>Background</p> <p>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 Kinase...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2011-05-01
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| Series: | Molecular Pain |
| Online Access: | http://www.molecularpain.com/content/7/1/34 |
| _version_ | 1818019154320424960 |
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| author | Shapiro Mark S Belugin Sergei Bal Manjot Chaudhury Sraboni Jeske Nathaniel A |
| author_facet | Shapiro Mark S Belugin Sergei Bal Manjot Chaudhury Sraboni Jeske Nathaniel A |
| author_sort | Shapiro Mark S |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.</p> |
| first_indexed | 2024-04-14T07:48:36Z |
| format | Article |
| id | doaj.art-189b0cc170b548fbb1798d145093ed16 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-04-14T07:48:36Z |
| publishDate | 2011-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-189b0cc170b548fbb1798d145093ed162022-12-22T02:05:16ZengSAGE PublishingMolecular Pain1744-80692011-05-01713410.1186/1744-8069-7-34AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulinShapiro Mark SBelugin SergeiBal ManjotChaudhury SraboniJeske Nathaniel A<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.</p>http://www.molecularpain.com/content/7/1/34 |
| spellingShingle | Shapiro Mark S Belugin Sergei Bal Manjot Chaudhury Sraboni Jeske Nathaniel A AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin Molecular Pain |
| title | AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin |
| title_full | AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin |
| title_fullStr | AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin |
| title_full_unstemmed | AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin |
| title_short | AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin |
| title_sort | akap150 mediated trpv1 sensitization is disrupted by calcium calmodulin |
| url | http://www.molecularpain.com/content/7/1/34 |
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