Regulation of NCX1 by palmitoylation

Fuller, W. and Gök, C. (2020) Regulation of NCX1 by palmitoylation. Cell Calcium, 86, 102158. (doi: 10.1016/j.ceca.2019.102158) (PMID:31935590)

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Abstract

Palmitoylation (S-acylation) is the reversible conjugation of a fatty acid (usually C16 palmitate) to intracellular cysteine residues of proteins via a thioester linkage. Palmitoylation anchors intracellular regions of proteins to membranes because the palmitoylated cysteine is recruited to the lipid bilayer. NCX1 is palmitoylated at a single cysteine in its large regulatory intracellular loop. The presence of an amphipathic α-helix immediately adjacent to the NCX1 palmitoylation site is required for NCX1 palmitoylation. The NCX1 palmitoylation site is conserved through most metazoan phlya. Although palmitoylation does not regulate the normal forward or reverse ion transport modes of NCX1, NCX1 palmitoylation is required for its inactivation: sodium-dependent inactivation and inactivation by PIP2 depletion are significantly impaired for unpalmitoylatable NCX1. Here we review the role of palmitoylation in regulating NCX1 activity, and highlight future questions that must be addressed to fully understand the importance of this regulatory mechanism for sodium and calcium transport in cardiac muscle.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Fuller, Dr Will and Gok, Mr Caglar
Authors: Fuller, W., and Gök, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Cell Calcium
Publisher:Elsevier
ISSN:0143-4160
ISSN (Online):1532-1991
Published Online:08 January 2020
Copyright Holders:Copyright © 2019 Elsevier Ltd.
First Published:First published in Cell Calcium 86:102158
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303370The role of NCX1 palmitoylation in cardiac functionWilliam FullerBritish Heart Foundation (BHF)SP/16/3/32317CAMS - Cardiovascular Science