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)

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, Dr 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303370		The role of NCX1 palmitoylation in cardiac function	William Fuller	British Heart Foundation (BHF)	SP/16/3/32317	CAMS - Cardiovascular Science