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Updated: Oct 30, 2025
Ligand Nano-cluster Arrays in a Supported Lipid Bilayer
Published on: April 23, 2017
RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains
Yong Zhou1, Alemayehu A Gorfe1, John F Hancock1
1Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX, United States.
Abstract:
RAS proteins are lipid-anchored small GTPases that switch between the GTP-bound active and GDP-bound inactive states. RAS isoforms, including HRAS, NRAS and splice variants KRAS4A and KRAS4B, are some of the most frequently mutated proteins in cancer. In particular, constitutively active mutants of KRAS comprise ∼80% of all RAS oncogenic mutations and are found in 98% of pancreatic, 45% of colorectal and 31% of lung tumors. Plasma membrane (PM) is the primary location of RAS signaling in biology and pathology. Thus, a better understanding of how RAS proteins localize to and distribute on the PM is critical to better comprehend RAS biology and to develop new strategies to treat RAS pathology. In this review, we discuss recent findings on how RAS proteins sort lipids as they undergo macromolecular assembly on the PM. We also discuss how RAS/lipid nanoclusters serve as signaling platforms for the efficient recruitment of effectors and signal transduction, and how perturbing the PM biophysical properties affect the spatial distribution of RAS isoforms and their functions.
Insights
RAS proteins, frequently mutated in cancer, are key to cell signaling at the plasma membrane. Understanding their lipid sorting and nanocluster formation is crucial for developing new cancer therapies.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- RAS proteins are small GTPases regulating cell signaling.
- Mutated RAS proteins, especially KRAS, are prevalent in various cancers.
- RAS signaling primarily occurs at the plasma membrane.
Purpose of the Study:
- To review recent findings on RAS protein localization and distribution on the plasma membrane.
- To explore how RAS proteins interact with lipids and form signaling platforms.
- To understand the impact of plasma membrane properties on RAS function.
Main Methods:
- Literature review of recent research on RAS protein biology.
- Analysis of studies on RAS protein-lipid interactions.
- Examination of research on plasma membrane biophysics and RAS signaling.
Main Results:
- RAS proteins sort lipids during their assembly on the plasma membrane.
- RAS/lipid nanoclusters act as signaling platforms for effector recruitment.
- Plasma membrane properties influence RAS isoform distribution and function.
Conclusions:
- Understanding RAS protein-lipid sorting and nanocluster formation is vital for comprehending RAS biology.
- Targeting RAS localization and signaling at the plasma membrane offers potential therapeutic strategies for cancer.
