4.6 Article

zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion Through Palmitoylation of Rab3gap1

Journal

JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 8, Issue 5, Pages 518-542

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2022.11.003

Keywords

atrial natriuretic peptide; heart failure; palmitoylation; Rab3; exocytosis

Ask authors/readers for more resources

Production and release of natriuretic peptides by the stressed heart can reduce cardiac workload and be targeted for the treatment of heart failure. However, the mechanisms regulating cardiomyocyte exocytosis and natriuretic peptide release are still unclear. Our study reveals a novel pathway involving zDHHC9-mediated palmitoylation of Rab3gap1, which impairs exocytosis and limits atrial natriuretic peptide release.
Production and release of natriuretic peptides by the stressed heart reduce cardiac workload by promoting vasodilation, natriuresis, and diuresis, which has been leveraged in the recent development of novel heart -failure pharmacotherapies, yet the mechanisms regulating cardiomyocyte exocytosis and natriuretic peptide release remain ill defined. We found that the Golgi S-acyltransferase zDHHC9 palmitoylates Rab3gap1 resulting in its spatial segregation from Rab3a, elevation of Rab3a-GTP levels, formation of Rab3a-positive peripheral vesicles, and impairment of exocytosis that limits atrial natriuretic peptide release. This novel pathway potentially can be exploited for targeting natriuretic peptide signaling in the treatment of heart failure. (J Am Coll Cardiol Basic Trans Science 2023;8:518-542) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available