Insulin-induced palmitoylation regulates the Cardiac Na+/Ca2+ Exchanger NCX1

Gok, C. , Robertson, A. D. and Fuller, W. (2022) Insulin-induced palmitoylation regulates the Cardiac Na+/Ca2+ Exchanger NCX1. Cell Calcium, 104, 102567. (doi: 10.1016/j.ceca.2022.102567) (PMID:35231700)

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Abstract

The cardiac Na+/Ca2+ Exchanger (NCX1) controls Ca2+ extrusion from the cytosol by mediating bidirectional exchange of Na+ for Ca2+, and therefore controls cardiac relaxation. Insulin regulates Ca2+ handling in cardiac tissue through NCX1, however how insulin changes NCX1 activity is poorly understood. Palmitoylation is the only post-translational modification identified to alter NCX1 activity. Here we show that insulin triggers local structural re-arrangements within existing NCX1 dimers by inducing their palmitoylation, thus tunes NCX1 inactivation through a zDHHC5-dependent mechanism in multiple cell types. By activating fatty acid and fatty acyl CoA synthesis insulin promotes palmitoylation of the zDHHC5 active site, which leads to enhanced NCX1 palmitoylation. Our findings represent a new mechanism to regulate the palmitoylation of numerous zDHHC5 substrates.

Item Type:Articles
Additional Information:We acknowledge financial support from the British Heart Foundation, grant reference SP/16/3/32317.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Fuller, Professor Will and Robertson, Dr Alan and Gok, Mr Caglar
Creator Roles:
Gok, C.Conceptualization, Formal analysis, Methodology, Writing – original draft
Fuller, W.Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review and editing
Robertson, A.Resources
Authors: Gok, C., Robertson, A. D., and Fuller, W.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cell Calcium
Publisher:Elsevier
ISSN:0143-4160
ISSN (Online):1532-1991
Published Online:26 February 2022
Copyright Holders:Copyright © 2022 The Authors.
First Published:First published in Cell Calcium 104:102567
Publisher Policy:Reproduced under a Creative Commons License

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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