POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.
EMBO Rep
; 23(12): e55208, 2022 12 06.
Article
em En
| MEDLINE
| ID: mdl-36254885
ABSTRACT
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 AC9POPDC1 complex and copurifies in a POPDC1-dependent manner with AC9 activity in heart. Although the AC9POPDC1 interaction is cAMP-independent, TREK-1 association with AC9 and POPDC1 is reduced upon stimulation of the ß-adrenergic receptor (ßAR). AC9 activity is required for ßAR reduction of TREK-1 complex formation with AC9POPDC1 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Adenilil Ciclases
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos