TY - JOUR
T1 - CaMKIIδ Splice Variants in the Healthy and Diseased Heart
AU - Duran, Javier
AU - Nickel, Lennart
AU - Estrada, Manuel
AU - Backs, Johannes
AU - van den Hoogenhof, Maarten M. G.
N1 - Funding Information: Funding. MH was supported by grants from the German Center for Cardiovascular Research (DZHK; grant# 81X3500122), the German Research Foundation (DFG; grant# HO 6446/1-1), and the German Society of Cardiology (DGK; grant# DGK02/2019). Publisher Copyright: © Copyright © 2021 Duran, Nickel, Estrada, Backs and van den Hoogenhof.
PY - 2021/3/11
Y1 - 2021/3/11
N2 - RNA splicing has been recognized in recent years as a pivotal player in heart development and disease. The Ca2+/calmodulin dependent protein kinase II delta (CaMKIIδ) is a multifunctional Ser/Thr kinase family and generates at least 11 different splice variants through alternative splicing. This enzyme, which belongs to the CaMKII family, is the predominant family member in the heart and functions as a messenger toward adaptive or detrimental signaling in cardiomyocytes. Classically, the nuclear CaMKIIδB and cytoplasmic CaMKIIδC splice variants are described as mediators of arrhythmias, contractile function, Ca2+ handling, and gene transcription. Recent findings also put CaMKIIδA and CaMKIIδ9 as cardinal players in the global CaMKII response in the heart. In this review, we discuss and summarize the new insights into CaMKIIδ splice variants and their (proposed) functions, as well as CaMKII-engineered mouse phenotypes and cardiac dysfunction related to CaMKIIδ missplicing. We also discuss RNA splicing factors affecting CaMKII splicing. Finally, we discuss the translational perspective derived from these insights and future directions on CaMKIIδ splicing research in the healthy and diseased heart.
AB - RNA splicing has been recognized in recent years as a pivotal player in heart development and disease. The Ca2+/calmodulin dependent protein kinase II delta (CaMKIIδ) is a multifunctional Ser/Thr kinase family and generates at least 11 different splice variants through alternative splicing. This enzyme, which belongs to the CaMKII family, is the predominant family member in the heart and functions as a messenger toward adaptive or detrimental signaling in cardiomyocytes. Classically, the nuclear CaMKIIδB and cytoplasmic CaMKIIδC splice variants are described as mediators of arrhythmias, contractile function, Ca2+ handling, and gene transcription. Recent findings also put CaMKIIδA and CaMKIIδ9 as cardinal players in the global CaMKII response in the heart. In this review, we discuss and summarize the new insights into CaMKIIδ splice variants and their (proposed) functions, as well as CaMKII-engineered mouse phenotypes and cardiac dysfunction related to CaMKIIδ missplicing. We also discuss RNA splicing factors affecting CaMKII splicing. Finally, we discuss the translational perspective derived from these insights and future directions on CaMKIIδ splicing research in the healthy and diseased heart.
KW - CaMKII delta
KW - RNA splicing
KW - heart
KW - splice variant
KW - therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85103114149&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcell.2021.644630
DO - https://doi.org/10.3389/fcell.2021.644630
M3 - Review article
C2 - 33777949
SN - 2296-634X
VL - 9
JO - Frontiers in cell and developmental biology
JF - Frontiers in cell and developmental biology
M1 - 644630
ER -