دورية أكاديمية
أعرض في EDS

POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.

التفاصيل البيبلوغرافية
العنوان: POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.
المؤلفون: Baldwin TA; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Li Y; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Marsden AN; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Rinné S; Institute for Physiology and Pathophysiology, Vegetative Physiology and Marburg Center for Mind, Brain and Behavior MCMBB, Philipps-University of Marburg, Marburg, Germany., Garza-Carbajal A; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Schindler RFR; National Heart and Lung Institute, Imperial College London, London, UK., Zhang M; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Garcia MA; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Venna VR; Department Neurology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA., Decher N; Institute for Physiology and Pathophysiology, Vegetative Physiology and Marburg Center for Mind, Brain and Behavior MCMBB, Philipps-University of Marburg, Marburg, Germany., Brand T; National Heart and Lung Institute, Imperial College London, London, UK., Dessauer CW; Department Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA.
المصدر: EMBO reports [EMBO Rep] 2022 Dec 06; Vol. 23 (12), pp. e55208. Date of Electronic Publication: 2022 Oct 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
مواضيع طبية MeSH: Adenylyl Cyclases*/genetics , Potassium Channels*
مستخلص: 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.
(©2022 The Authors. Published under the terms of the CC BY 4.0 license.)
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معلومات مُعتمدة: R35 GM145291 United States GM NIGMS NIH HHS; PG/19/13/34247 United Kingdom BHF_ British Heart Foundation; PG/14/46/30911 United Kingdom BHF_ British Heart Foundation; R01 GM060419 United States GM NIGMS NIH HHS; R37 NS096493 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: ADCY9; BVES; TREK-1; adenylyl cyclase; heart rate variability
المشرفين على المادة: EC 4.6.1.1 (Adenylyl Cyclases)
0 (Potassium Channels)
تواريخ الأحداث: Date Created: 20221018 Date Completed: 20221215 Latest Revision: 20230621
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9724675
DOI: 10.15252/embr.202255208
PMID: 36254885
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-3178
DOI:10.15252/embr.202255208