Defects in Cytoskeletal Signaling Pathways, Arrhythmia, and Sudden Cardiac Death

Ankyrin polypeptides are cellular adapter proteins that tether integral membrane proteins to the cytoskeleton in a host of human organs. Initially identified as integral components of the cytoskeleton in erythrocytes, a recent explosion in ankyrin research has demonstrated that these proteins play prominent roles in cytoskeletal signaling pathways and membrane protein trafficking/regulation in a variety of excitable and non-excitable cells including heart and brain. Importantly, ankyrin research has translated from bench to bedside with the discovery of human gene variants associated with ventricular arrhythmias that alter ankyrin–based pathways. Ankyrin polypeptides have also been found to play an instrumental role in various forms of sinus node disease and atrial fibrillation (AF). Mouse models of ankyrin-deficiency have played fundamental roles in the translation of ankyrin-based research to new clinical understanding of human sinus node disease, AF, and ventricular tachycardia.

• Publication year

  2012

• Venue

  Front. Physio.

• Publication date

  2012-04-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fphys.2012.00122PMID 22586405PMCID 3343379
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity.

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• Defects in Ankyrin-Based Membrane Protein Targeting Pathways Underlie Atrial Fibrillation

  2011cited by this paper
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• EH Domain Proteins Regulate Cardiac Membrane Protein Targeting

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• Defining new insight into atypical arrhythmia: a computational model of ankyrin-B syndrome.

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• Functional anatomy of the murine sinus node: high-resolution optical mapping of ankyrin-B heterozygous mice.

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• Ankyrin-B Regulates Kir6.2 Membrane Expression and Function in Heart*

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• A β(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice.

  2010influential reference
• Regulation of the ankyrin-B-based targeting pathway following myocardial infarction.

  2009cited by this paper
• Membrane domains based on ankyrin and spectrin associated with cell-cell interactions.

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• Cardiac ankyrins in health and disease.

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  2007cited by this paper
• Molecular basis for PP2A regulatory subunit B56alpha targeting in cardiomyocytes.

  2007influential reference
• Isoform Specificity of Ankyrin-B

  2006cited by this paper
• Cardiac ankyrins: Essential components for development and maintenance of excitable membrane domains in heart.

  2006cited by this paper
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  2005cited by this paper
• Brugada syndrome: report of the second consensus conference.

  2005cited by this paper
• Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association.

  2005cited by this paper
• Ankyrin-B Targets β2-Spectrin to an Intracellular Compartment in Neonatal Cardiomyocytes*

  2004influential reference
• A cardiac arrhythmia syndrome caused by loss of ankyrin-B function

  2004cited by this paper
• Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes.

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• Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death

  2003influential reference
• Obscurin is a ligand for small ankyrin 1 in skeletal muscle.

  2003cited by this paper
• Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. role of phosphatase 2A.

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  2001cited by this paper
• Ankyrins and cellular targeting of diverse membrane proteins to physiological sites.

  2001influential reference
• Abnormal cardiac Na(+) channel properties and QT heart rate adaptation in neonatal ankyrin(B) knockout mice.

  2000cited by this paper
• Spectrum of Mutations in Long-QT Syndrome Genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2

  2000influential reference
• Survey of cardiac pacing in the United States in 1989.

  1992cited by this paper
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  1979cited by this paper

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• Murine Electrophysiological Models of Cardiac Arrhythmogenesis.

  2017cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
• Cardiomyocyte protein trafficking: Relevance to heart disease and opportunities for therapeutic intervention.

  2015cites this paper
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  2014cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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