Calmodulin (CaM) and CaMKII Signaling in Heart

Calmodulin (CaM) and CaMKII signaling in heart have emerged as critical regulators of cardiac ion channels, electrophysiology, Ca handling, contractile regulation and gene transcription and downstream targets of numerous G-protein coupled receptor pathways in the past 15 years. Our group has contributed greatly to this realization and uncovered numerous molecular mechanistic pathways by which this occurs. This includes measuring dynamics of Ca-CaM and CaMKII activation in different cellular domains (and by different activators), identifying novel mechanisms of post-translational CaMKII modifications (via O-GlycNAcylation and nitrosylation) that promote chronic CaMKII activation (e.g., in HF diabetes and beta-adrenergic activation).  Our 100 papers on CaM and CaMKII signaling in heart have had major impact in the cardiac field.

 

1. Maier LS, Zhang T, Chen L, DeSantiago J, Li Y, Brown JH, Bers DM:  Transgenic CaMKII-deltaC overexpression uniquely alters cardiac myocyte Ca handling: reduced SR Ca load, but increased fractional release.  Circ. Res. 92: 904-911, 2003.

2. Erickson JR, Patel R, Ferguson A, Bossuyt J, Bers DM. Fluorescence resonance energy transfer-based sensor Camui provides new insight into mechanisms of calcium/calmodulin-dependent protein kinase II activation in intact cardiomyocytes. Circ Res. 109:729-738, 2011.

3. Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K, Copeland RJ, Despa F, Hart GW, Ripplinger CM, Bers DM. Diabetic hyperglycemia activates CaMKII and arrhythmias by O-linked glycosylation.  Nature, 502:372-376, 2013.

4. Uchinoumi H, Yang Y,1 Oda T, Li N, Alsina KM, Puglisi JL, Chen-Izu Y, Cornea RL, Wehrens XHT, Bers DM. CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift. J Mol Cell Cardiol. 98:62-72, 2016.

5. Simon M, Ko CY, Rebbeck RT, Baidar S, Cornea RL, Bers DM.  Post-Translational Modifications Increase CaMKIIδ Affinity for Calmodulin in Cardiac Ventricular Myocytes. J Mol Cell Cardiol, 161:53-61, 2021.

6. Hegyi B, Fasoli A, Ko CY, Van BW, Alim CC, ShenEY, Ciccozzi MM, Tapa S, Ripplinger CM, Erickson JR, Bossuyt J, Bers DM. CaMKII Serine 280 O-GlcNAcylation Links Diabetic Hyperglycemia to Proarrhythmia. Circ Res, 129:98-113, 2021.