H-ras distribution and signaling in plasma membrane microdomains are regulated by acylation and deacylation events

Molecular and Cellular Biology
Lorena Agudo-IbáñezPiero Crespo

Abstract

H-Ras must adhere to the plasma membrane to be functional. This is accomplished by posttranslational modifications, including palmitoylation, a reversible process whereby H-Ras traffics between the plasma membrane and the Golgi complex. At the plasma membrane, H-Ras has been proposed to occupy distinct sublocations, depending on its activation status: lipid rafts/detergent-resistant membrane fractions when bound to GDP, diffusing to disordered membrane/soluble fractions in response to GTP loading. Herein, we demonstrate that H-Ras sublocalization is dictated by its degree of palmitoylation in a cell type-specific manner. Whereas H-Ras localizes to detergent-resistant membrane fractions in cells with low palmitoylation activity, it locates to soluble membrane fractions in lineages where it is highly palmitoylated. Interestingly, in both cases GTP loading results in H-Ras diffusing away from its original sublocalization. Moreover, tilting the equilibrium between palmitoylation and depalmitoylation processes can substantially alter H-Ras segregation and, subsequently, its biochemical and biological functions. Thus, the palmitoylation/depalmitoylation balance not only regulates H-Ras cycling between endomembranes and the plasma mem...Continue Reading

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Citations

Apr 22, 2016·Molecular Biology of the Cell·Ana HerreroPiero Crespo
Feb 23, 2019·EMBO Reports·Jewon JungKartik Venkatachalam
May 3, 2018·Oncotarget·Joanna PodkalickaAleksander F Sikorski
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Aug 25, 2017·Traffic·Jose L DaniottiJavier Valdez Taubas
Apr 4, 2020·Molecular Cancer Therapeutics·Lihua ShuZhuo G Chen
Oct 24, 2020·Journal of Cellular Physiology·Jiayu JinDan Meng
Apr 6, 2021·Frontiers in Molecular Biosciences·Carla Busquets-Hernández, Gemma Triola
Jun 3, 2021·Genes·Alberto Fernández-MedardeEugenio Santos
Dec 6, 2018·Journal of the American Chemical Society·Andrew K RuddNeal K Devaraj
Sep 2, 2021·Biophysics Reviews·Ruth NussinovHyunbum Jang

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