Dual roles of the A kinase-anchoring protein Yotiao in the modulation of a cardiac potassium channel: a passive adaptor versus an active regulator.

European Journal of Cell Biology
Lei Chen, Robert S Kass

Abstract

Cardiac function is regulated critically by the autonomic nervous system to adapt to the physical activity and emotional stress. A slowly activating cardiac potassium channel (I(Ks)) is modulated by stimulation of the sympathetic nervous system (SNS) and contributes to cardiac action potential shortening in the face of concomitant increases in heart rate. Activation of beta-adrenergic receptors in response to SNS stimulation results in protein kinase A (PKA)-mediated phosphorylation of I(Ks) channels. We have found that the functional regulation of the I(Ks) channel by PKA requires the A kinase-anchoring protein (AKAP) Yotiao. Yotiao forms a macromolecular complex with the channel and recruits key enzymes such as PKA and protein phosphatase 1 (PP1) to control the phosphorylation state of I(Ks). Our recent findings revealed a more active role of Yotiao in the PKA modulation of I(Ks). We found that Yotiao participates actively in translating the phosphorylation-induced change into altered channel activity. Moreover Yotiao itself can be phosphorylated by PKA upon beta-adrenergic stimulation. Ablation of Yotiao phosphorylation impairs PKA-induced changes in I(Ks) voltage-dependent activation and current kinetics. Taken together we ...Continue Reading

References

Feb 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Junko KurokawaRobert S Kass
Sep 24, 2004·Molecular Cell·Graeme K CarnegieJohn D Scott
Nov 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Junko KurokawaRobert S Kass

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Citations

Sep 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Leslie A PiggottCarmen W Dessauer
Sep 3, 2011·Journal of Cardiovascular Pharmacology·Lei Chen, Robert S Kass
Nov 1, 2007·Journal of Molecular Signaling·Alexandra V AndreevaTatyana A Voyno-Yasenetskaya
Jul 21, 2015·Journal of Proteomics·Indu ChoudharyEuikyung Kim
Jan 4, 2013·Circulation·Gregory Webster, Charles I Berul
Apr 21, 2007·The EMBO Journal·Caleb RichterGreg Odorizzi
Jun 10, 2011·Journal of Cardiovascular Pharmacology·Alessandra Stangherlin, Manuela Zaccolo
Oct 12, 2007·Physiology·Peter J Mohler, Xander H T Wehrens
Apr 24, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Ralph J van Oort, Xander H T Wehrens
Jul 23, 2020·Frontiers in Physiology·Jennifer van der HorstThomas A Jepps
Mar 24, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Claudia SeylerEdgar Zitron
Dec 19, 2020·Pharmacological Reviews·Manuela ZaccoloMiguel J Lobo

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