Dynamic Palmitoylation of the Sodium-Calcium Exchanger Modulates Its Structure, Affinity for Lipid-Ordered Domains, and Inhibition by XIP.
acylation
calcium
ion transport
lipid raft
sodium
thioesterase
zDHHC
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
03
01
2020
revised:
07
04
2020
accepted:
06
05
2020
entrez:
11
6
2020
pubmed:
11
6
2020
medline:
20
5
2021
Statut:
ppublish
Résumé
The transmembrane sodium-calcium (Na-Ca) exchanger 1 (NCX1) regulates cytoplasmic Ca levels by facilitating electrogenic exchange of Ca for Na. Palmitoylation, the only reversible post-translational modification known to modulate NCX1 activity, controls NCX1 inactivation. Here, we show that palmitoylation of NCX1 modifies the structural arrangement of the NCX1 dimer and controls its affinity for lipid-ordered membrane domains. NCX1 palmitoylation occurs dynamically at the cell surface under the control of the enzymes zDHHC5 and APT1. We identify the position of the endogenous exchange inhibitory peptide (XIP) binding site within the NCX1 regulatory intracellular loop and demonstrate that palmitoylation controls the ability of XIP to bind this site. We also show that changes in NCX1 palmitoylation change cytosolic Ca. Our results thus demonstrate the broad molecular consequences of NCX1 palmitoylation and highlight a means to manipulate the inactivation of this ubiquitous ion transporter that could ameliorate pathologies linked to Ca overload via NCX1.
Identifiants
pubmed: 32521252
pii: S2211-1247(20)30650-1
doi: 10.1016/j.celrep.2020.107697
pmc: PMC7296346
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
LAMTOR5 protein, human
0
Sodium-Calcium Exchanger
0
sodium-calcium exchanger 1
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107697Subventions
Organisme : British Heart Foundation
ID : PG/18/60/33957
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/19/5/34150
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/16/3/32317
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/68/30988
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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