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POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart
The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain‐containing (POPDC) protein. The POPDC f...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724675/ https://www.ncbi.nlm.nih.gov/pubmed/36254885 http://dx.doi.org/10.15252/embr.202255208 |
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author | Baldwin, Tanya A Li, Yong Marsden, Autumn N Rinné, Susanne Garza‐Carbajal, Anibal Schindler, Roland F R Zhang, Musi Garcia, Mia A Venna, Venugopal Reddy Decher, Niels Brand, Thomas Dessauer, Carmen W |
author_facet | Baldwin, Tanya A Li, Yong Marsden, Autumn N Rinné, Susanne Garza‐Carbajal, Anibal Schindler, Roland F R Zhang, Musi Garcia, Mia A Venna, Venugopal Reddy Decher, Niels Brand, Thomas Dessauer, Carmen W |
author_sort | Baldwin, Tanya A |
collection | PubMed |
description | The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain‐containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP‐dependent binding and regulation of TREK‐1 potassium channels. We show that TREK‐1 binds the AC9:POPDC1 complex and copurifies in a POPDC1‐dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP‐independent, TREK‐1 association with AC9 and POPDC1 is reduced upon stimulation of the β‐adrenergic receptor (βAR). AC9 activity is required for βAR reduction of TREK‐1 complex formation with AC9:POPDC1 and in reversing POPDC1 enhancement of TREK‐1 currents. Finally, deletion of the gene‐encoding AC9 (Adcy9) gives rise to bradycardia at rest and stress‐induced heart rate variability, a milder phenotype than the loss of Popdc1 but similar to the loss of Kcnk2 (TREK‐1). Thus, POPDC1 represents a novel adaptor for AC9 interactions with TREK‐1 to regulate heart rate control. |
format | Online Article Text |
id | pubmed-9724675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97246752022-12-08 POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart Baldwin, Tanya A Li, Yong Marsden, Autumn N Rinné, Susanne Garza‐Carbajal, Anibal Schindler, Roland F R Zhang, Musi Garcia, Mia A Venna, Venugopal Reddy Decher, Niels Brand, Thomas Dessauer, Carmen W EMBO Rep Articles The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain‐containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP‐dependent binding and regulation of TREK‐1 potassium channels. We show that TREK‐1 binds the AC9:POPDC1 complex and copurifies in a POPDC1‐dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP‐independent, TREK‐1 association with AC9 and POPDC1 is reduced upon stimulation of the β‐adrenergic receptor (βAR). AC9 activity is required for βAR reduction of TREK‐1 complex formation with AC9:POPDC1 and in reversing POPDC1 enhancement of TREK‐1 currents. Finally, deletion of the gene‐encoding AC9 (Adcy9) gives rise to bradycardia at rest and stress‐induced heart rate variability, a milder phenotype than the loss of Popdc1 but similar to the loss of Kcnk2 (TREK‐1). Thus, POPDC1 represents a novel adaptor for AC9 interactions with TREK‐1 to regulate heart rate control. John Wiley and Sons Inc. 2022-10-18 /pmc/articles/PMC9724675/ /pubmed/36254885 http://dx.doi.org/10.15252/embr.202255208 Text en ©2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Baldwin, Tanya A Li, Yong Marsden, Autumn N Rinné, Susanne Garza‐Carbajal, Anibal Schindler, Roland F R Zhang, Musi Garcia, Mia A Venna, Venugopal Reddy Decher, Niels Brand, Thomas Dessauer, Carmen W POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart |
title | POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart |
title_full | POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart |
title_fullStr | POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart |
title_full_unstemmed | POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart |
title_short | POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK‐1 in heart |
title_sort | popdc1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel trek‐1 in heart |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724675/ https://www.ncbi.nlm.nih.gov/pubmed/36254885 http://dx.doi.org/10.15252/embr.202255208 |
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