Greasing the wheels or a spanner in the works? Regulation of the cardiac sodium pump by palmitoylation

Jacqueline Howie, Krzysztof J. Wypijewski, Fiona Plain, Lindsay Tulloch, Niall J. Fraser, William Fuller (Lead / Corresponding author)

Research output: Contribution to journalReview article

3 Citations (Scopus)
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Abstract

The ubiquitous sodium / potassium ATPase (Na pump) is the most abundant primary active transporter at the cell surface of multiple cell types, including ventricular myocytes in the heart. The activity of the Na pump establishes transmembrane ion gradients that control numerous events at the cell surface, positioning it as a key regulator of the contractile and metabolic state of the myocardium. Defects in Na pump activity and regulation elevate intracellular Na in cardiac muscle, playing a causal role in the development of cardiac hypertrophy, diastolic dysfunction, arrhythmias and heart failure. Palmitoylation is the reversible conjugation of the fatty acid palmitate to specific protein cysteine residues; all subunits of the cardiac Na pump are palmitoylated. Palmitoylation of the pump’s accessory subunit phospholemman by the cell surface palmitoyl acyl transferase DHHC5 leads to pump inhibition, possibly by altering the relationship between the pump catalytic α subunit and specifically bound membrane lipids. In this review we discuss the functional impact of phospholemman palmitoylation on the cardiac Na pump and the molecular basis of recognition of phospholemman by its palmitoylating enzyme DHHC5, as well as effects of palmitoylation on Na pump cell surface abundance in the cardiac muscle. We also highlight the numerous unanswered questions regarding the cellular control of this fundamentally important regulatory process.
Original languageEnglish
Pages (from-to)175-191
Number of pages17
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume53
Issue number2
Early online date9 Feb 2018
DOIs
Publication statusPublished - 4 Mar 2018

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Keywords

  • Acylation
  • DHHC
  • Palmitoyl acyl transferase
  • Thioesterase
  • Posttranslational modification
  • P-type ATPase
  • Ion transport
  • Phospholemman
  • palmitoyl acyl transferase
  • ion transport
  • post-translational modification
  • phospholemman
  • thioesterase
  • Humans
  • Membrane Proteins/genetics
  • Heart Ventricles/enzymology
  • Palmitic Acid/metabolism
  • Sodium-Potassium-Exchanging ATPase/genetics
  • Ion Transport/genetics
  • Myocardium/enzymology
  • Lipoylation
  • Heart Diseases/enzymology
  • Myocytes, Cardiac/enzymology
  • Phosphoproteins/genetics
  • Animals

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