Individual S-acylated cysteines differentially contribute to H-Ras endomembrane traffcking and acylation/deacylation cycles

Pedro, Maria P. , Vilcaes, Aldo A. , Gomez, Guillermo A. and Daniotti, Jose L. (2017) Individual S-acylated cysteines differentially contribute to H-Ras endomembrane traffcking and acylation/deacylation cycles. Molecular Biology of the Cell, 28 7: 962-974. doi:10.1091/mbc.E16-08-0603


Author Pedro, Maria P.
Vilcaes, Aldo A.
Gomez, Guillermo A.
Daniotti, Jose L.
Title Individual S-acylated cysteines differentially contribute to H-Ras endomembrane traffcking and acylation/deacylation cycles
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1939-4586
1059-1524
Publication date 2017-04-01
Sub-type Article (original research)
DOI 10.1091/mbc.E16-08-0603
Open Access Status Not yet assessed
Volume 28
Issue 7
Start page 962
End page 974
Total pages 13
Place of publication Bethesda, MD, United States
Publisher American Society for Cell Biology
Collection year 2018
Language eng
Abstract S-acylation/deacylation cycles and vesicular transport are critical for an adequate subcellular distribution of S-acylated Ras proteins. H-Ras is dually acylated on cysteines 181 and 184, but it is unknown how these residues individually contribute to H-Ras traffcking. In this study, we characterized the acylation and deacylation rates and membrane traffcking of monoacylated H-Ras mutants to analyze their contributions to H-Ras plasma membrane and endomembrane distribution. We demonstrated that dually acylated H-Ras interacts with acylprotein thioesterases (APTs) 1 and 2 at the plasma membrane. Moreover, single-acylation mutants of H-Ras differed not only in their subcellular distribution, where both proteins localized to different extents at both the Golgi complex and plasma membrane, but also in their deacylation rates, which we showed to be due to different sensitivities to APT1 and APT2. Fluorescence photobleaching and photoactivation experiments also revealed that 1) although S-acylated, single-acylation mutants are incorporated with different effciencies into Golgi complex to plasma membrane vesicular carriers, and 2) the different deacylation rates of single-acylated H-Ras influence differentially its overall exchange between different compartments by nonvesicular transport. Taken together, our results show that individual S-acylation sites provide singular information about H-Ras subcellular distribution that is required for GTPase signaling.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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