Gök, C. , Main, A., Gao, X., Kerekes, Z., Plain, F., Kuo, C.-W., Robertson, A. D., Fraser, N. J. and Fuller, W. (2021) Insights into the molecular basis of the palmitoylation and depalmitoylation of NCX1. Cell Calcium, 97, 102408. (doi: 10.1016/j.ceca.2021.102408) (PMID:33873072)
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Abstract
Catalyzed by zDHHC-PAT enzymes and reversed by thioesterases, protein palmitoylation is the only post-translational modification recognized to regulate the sodium/calcium exchanger NCX1. NCX1 palmitoylation occurs at a single site at position 739 in its large regulatory intracellular loop. An amphipathic ɑ-helix between residues 740-756 is a critical for NCX1 palmitoylation. Given the rich background of the structural elements involving in NCX1 palmitoylation, the molecular basis of NCX1 palmitoylation is still relatively poorly understood. Here we found that (1) the identity of palmitoylation machinery of NCX1 controls its spatial organization within the cell, (2) the NCX1 amphipathic ɑ-helix directly interacts with zDHHC-PATs, (3) NCX1 is still palmitoylated when it is arrested in either Golgi or ER, indicating that NCX1 is a substrate for multiple zDHHC-PATs, (4) the thioesterase APT1 but not APT2 as a part of NCX1-depalmitoylation machinery governs subcellular organization of NCX1, (5) APT1 catalyzes NCX1 depalmitoylation in the Golgi but not in the ER. We also report that NCX2 and NCX3 are dually palmitoylated, with important implications for substrate recognition and enzyme catalysis by zDHHC-PATs. Our results could support new molecular or pharmacological strategies targeting the NCX1 palmitoylation and depalmitoylation machinery.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Fraser, Dr Niall and Fuller, Professor Will and Gok, Dr Caglar and GAO, Xing and Kuo, Dr Chien-Wen and Main, Miss Alice |
Authors: | Gök, C., Main, A., Gao, X., Kerekes, Z., Plain, F., Kuo, C.-W., Robertson, A. D., Fraser, N. J., and Fuller, W. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Life Sciences |
Journal Name: | Cell Calcium |
Publisher: | Elsevier |
ISSN: | 0143-4160 |
ISSN (Online): | 1532-1991 |
Published Online: | 08 April 2021 |
Copyright Holders: | Copyright © 2021 The Authors |
First Published: | First published in Cell Calcium 97 :102408 |
Publisher Policy: | Reproduced under a Creative Commons License |
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