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

Howie, J., Wypijewski, K. J., Plain, F., Tulloch, L. B., Fraser, N. J. and Fuller, W. (2018) Greasing the wheels or a spanner in the works? Regulation of the cardiac sodium pump by palmitoylation. Critical Reviews in Biochemistry and Molecular Biology, 53(2), pp. 175-191. (doi: 10.1080/10409238.2018.1432560) (PMID:29424237)

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 (PLM) 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 PLM palmitoylation on the cardiac Na pump and the molecular basis of recognition of PLM 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fuller, Professor Will and Howie, Dr Jacqueline
• Authors: Howie, J., Wypijewski, K. J., Plain, F., Tulloch, L. B., Fraser, N. J., and Fuller, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Critical Reviews in Biochemistry and Molecular Biology
• Publisher: Taylor & Francis
• ISSN: 1040-9238
• ISSN (Online): 1549-7798
• Published Online: 09 February 2018
• Copyright Holders: Copyright © 2018 Informa UK Limited, trading as Taylor & Francis Group
• First Published: First published in Critical Reviews in Biochemistry and Molecular Biology 53(2):175-191
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher