Abstract
Ankyrin-B (encoded by ANK2), originally identified as a key cytoskeletal-associated protein in the brain, is highly expressed in the heart and plays critical roles in cardiac physiology and cell biology. In the heart, ankyrin-B plays key roles in the targeting and localization of key ion channels and transporters, structural proteins, and signaling molecules. The role of ankyrin-B in normal cardiac function is illustrated in animal models lacking ankyrin-B expression, which display significant electrical and structural phenotypes and life-threatening arrhythmias. Further, ankyrin-B dysfunction has been associated with cardiac phenotypes in humans (now referred to as “ankyrin-B syndrome”) including sinus node dysfunction, heart rate variability, atrial fibrillation, conduction block, arrhythmogenic cardiomyopathy, structural remodeling, and sudden cardiac death. Here, we review the diverse roles of ankyrin-B in the vertebrate heart with a significant focus on ankyrin-B-linked cell- and molecular-pathways and disease.
Highlights
Ankyrin ProteinsThe ankyrin family of polypeptides was first identified in the erythrocyte plasma membrane in 1979 by Bennett and Stenbuck [1]
Through the use of a canine cardiomyocyte model, Chu et al predicted that mislocalization of the Na+/K+ ATPase (NKA) and its subsequent uncoupling from the Na+/Ca2+ exchanger (NCX) in AnkB+/− cardiomyocytes disturbs Ca2+ and Na+ currents to predispose the cell to action potential prolongation [42]
Canonical ankyrin proteins share a similar structure composed of an membrane-binding domain (MBD), spectrin-binding domain (SBD), and a regulatory domain (RD) that is comprised of a death domain (DD) and C-terminal domain (CTD) (Figure 1)
Summary
The ankyrin family of polypeptides was first identified in the erythrocyte plasma membrane in 1979 by Bennett and Stenbuck [1]. SR = sarcoplasmic reticulum, AIS = axon initial segments, NKA = Na+/K+ ATPase, PP2A = protein phosphatase 2A, NCX = Na+/Ca2+ exchanger, Kir6.2 = inward rectifier potassium channel, CaV1.3 = voltage-gated calcium channel, L1CAMs = L1 family of neural cell adhesion molecules, SCD = sudden cardiac death, SND = sinus node disease, AF = atrial fibrillation, LQTS = long QT syndrome, VT = ventricular tachycardia, ARVC = arrhythmogenic right ventricular cardiomyopathy. AnkB and AnkG have similar structures, AnkG partners with proteins at the intercalated disc, including plakophilin-2 [23] and NaV1.5 [14], while AnkB is crucial for the expression and localization of ion channels at the sarcoplasmic reticulum, transverse-tubules, and plasma membrane [12]. Additional mechanisms underlying ankyrin specificity in vivo are a key area for future research
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
