Artículos de revistas
CaMKIId Splice variants in the healthy and diseased heart
Frontiers in Cell and Developmental Biology March 2021, Volume 9, Article 644630
Estrada Hormazábal, Manuel Iván
Van den Hoogenhof, Maarten M. G.
RNA splicing has been recognized in recent years as a pivotal player in heart development and disease. The Ca2C/calmodulin dependent protein kinase II delta (CaMKIId) 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 CaMKIIdB and cytoplasmic CaMKIIdC splice variants are described as mediators of arrhythmias, contractile function, Ca2C handling, and gene transcription. Recent findings also put CaMKIIdA and CaMKIId9 as cardinal players in the global CaMKII response in the heart. In this review, we discuss and summarize the new insights into CaMKIId splice variants and their (proposed) functions, as well as CaMKII-engineered mouse phenotypes and cardiac dysfunction related to CaMKIId missplicing. We also discuss RNA splicing factors affecting CaMKII splicing. Finally, we discuss the translational perspective derived from these insights and future directions on CaMKIId splicing research in the healthy and diseased heart.