RAS GTPases and Interleaflet Coupling in the Plasma Membrane

Authors

Junchen Liu
Neha Arora
Yong Zhou

Publication Date

9-1-2023

Journal

Cold Spring Harbor Perspectives in Biology

DOI

10.1101/cshperspect.a041414

PMID

37463719

PMCID

PMC10513163

PubMedCentral® Posted Date

9-15-2023

PubMedCentral® Full Text Version

Post-print

Abstract

RAS genes are frequently mutated in cancer. The primary signaling compartment of wild-type and constitutively active oncogenic mutant RAS proteins is the inner leaflet of the plasma membrane (PM). Thus, a better understanding of the unique environment of the PM inner leaflet is important to shed further light on RAS function. Over the past few decades, an integrated approach of superresolution imaging, molecular dynamic simulations, and biophysical assays has yielded new insights into the capacity of RAS proteins to sort lipids with specific headgroups and acyl chains, to assemble signaling nanoclusters on the inner PM. RAS proteins also sense and respond to changes in components of the outer PM leaflet, including glycophosphatidylinositol-anchored proteins, sphingophospholipids, glycosphingolipids, and galectins, as well as cholesterol that translocates between the two leaflets. Such communication between the inner and outer leaflets of the PM, called interleaflet coupling, allows RAS to potentially integrate extracellular mechanical and electrostatic information with intracellular biochemical signaling events, and reciprocally allows mutant RAS-transformed tumor cells to modify tumor microenvironments. Here, we review RAS-lipid interactions and speculate on potential mechanisms that allow communication between the opposing leaflets of the PM.

Keywords

Humans, ras Proteins, Cell Membrane, Neoplasms, Signal Transduction, Tumor Microenvironment

Published Open-Access

yes

Recommended Citation

Junchen Liu, Neha Arora, and Yong Zhou, "RAS GTPases and Interleaflet Coupling in the Plasma Membrane" (2023). Faculty, Staff and Student Publications. 5225.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5225