Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload

Yasuhiro Akazawa, Manabu Taneike, Hiromichi Ueda, Rika Kitazume-Taneike, Tomokazu Murakawa, Ryuta Sugihara, Hiroki Yorifuji, Hiroki Nishida, Kentaro Mine, Ayana Hioki, Shigemiki Omiya, Hiroyuki Nakayama, Osamu Yamaguchi, Tamotsu Yoshimori, Yasushi Sakata, Kinya Otsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Heart failure has high morbidity and mortality in the developed countries. Autophagy is important for the quality control of proteins and organelles in the heart. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) has been identified as a potent negative regulator of autophagy and endolysosomal trafficking. The aim of this study was to investigate the in vivo role of Rubicon-mediated autophagy and endosomal trafficking in the heart. We generated cardiomyocyte-specific Rubicon-deficient mice and subjected the mice to pressure overload by means of transverse aortic constriction. Rubicon-deficient mice showed heart failure with left ventricular dilatation, systolic dysfunction and lung congestion one week after pressure overload. While autophagic activity was unchanged, the protein amount of beta-1 adrenergic receptor was decreased in the pressure-overloaded Rubicon-deficient hearts. The increases in heart rate and systolic function by beta-1 adrenergic stimulation were significantly attenuated in pressure-overloaded Rubicon-deficient hearts. In isolated rat neonatal cardiomyocytes, the downregulation of the receptor by beta-1 adrenergic agonist was accelerated by knockdown of Rubicon through the inhibition of recycling of the receptor. Taken together, Rubicon protects the heart from pressure overload. Rubicon maintains the intracellular recycling of beta-1 adrenergic receptor, which might contribute to its cardioprotective effect.

Original languageEnglish
Article number41
JournalScientific Reports
Volume12
Issue number1
Early online date7 Jan 2022
DOIs
Publication statusE-pub ahead of print - 7 Jan 2022

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