Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jan 31;10(2):211.
doi: 10.3390/biom10020211.

Mechanisms and Alterations of Cardiac Ion Channels Leading to Disease: Role of Ankyrin-B in Cardiac Function

Holly C Sucharski  1   2 , Emma K Dudley  1   2 , Caullin B R Keith  1   2 , Mona El Refaey  1   2 , Sara N Koenig  1   2 , Peter J Mohler  1   2
Affiliations
Review

Mechanisms and Alterations of Cardiac Ion Channels Leading to Disease: Role of Ankyrin-B in Cardiac Function

Holly C Sucharski et al. Biomolecules. .

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.

Keywords: ANK2; ankyrin-B; cardiovascular disease; ion channels.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of canonical ankyrin-B. Canonical ankyrin proteins share four domains: a membrane-binding domain (MBD), spectrin-binding domain (SBD), death domain (DD), and C-terminal domain (CTD). The MBD consists of 24 ANK repeats that are defined by their secondary structure and aid in protein folding regulation. The SBD consists of ZU5N, ZU5C, and UPA domains that are important for binding βII-spectrin and supporting cardiomyocyte structure. The DD and CTD comprise the regulatory domain.
Figure 2
Figure 2
Representative diagram of ankyrin-B-binding partners to emphasize the importance of AnkB in the localization of ion channels, transporters, pumps, and structural proteins for proper cardiomyocyte function.
See this image and copyright information in PMC

References

    1. Bennett V., Stenbuck P.J. Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin. J. Biol. Chem. 1979;254:2533–2541. - PubMed
    1. Bennett V., Davis J., Fowler W.E. Immunoreactive forms of erythrocyte spectrin and ankyrin in brain. Philos. Trans. R. Soc. Lond. Ser. Biol. Sci. 1982;299:301–312. doi: 10.1098/rstb.1982.0134. - DOI - PubMed
    1. Bennett V., Davis J. Spectrin and ankyrin in brain. Cell Motil. 1983;3:623–633. doi: 10.1002/cm.970030527. - DOI - PubMed
    1. Davis J.Q., Bennett V. Brain ankyrin. Purification of a 72,000 Mr spectrin-binding domain. J. Biol. Chem. 1984;259:1874–1881. - PubMed
    1. Moon R.T., Ngai J., Wold B.J., Lazarides E. Tissue-specific expression of distinct spectrin and ankyrin transcripts in erythroid and nonerythroid cells. J. Cell Biol. 1985;100:152–160. doi: 10.1083/jcb.100.1.152. - DOI - PMC - PubMed

Publication types