Ras Multimers on the Membrane: Many Ways for a Heart-to-Heart Conversation

E Sila Ozdemir,Xiaolin Nan,Anna M Koester

doi:10.3390/genes13020219

Abstract

Formation of Ras multimers, including dimers and nanoclusters, has emerged as an exciting, new front of research in the ‘old’ field of Ras biomedicine. With significant advances made in the past few years, we are beginning to understand the structure of Ras multimers and, albeit preliminary, mechanisms that regulate their formation in vitro and in cells. Here we aim to synthesize the knowledge accrued thus far on Ras multimers, particularly the presence of multiple globular (G-) domain interfaces, and discuss how membrane nanodomain composition and structure would influence Ras multimer formation. We end with some general thoughts on the potential implications of Ras multimers in basic and translational biology.

Highlights

We focus on anionic lipids, phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylserine (PS), which have been shown to interact with both the Hyper-variable Region (HVR) and the G-domain of Ras on model membranes
Since our last review on this topic [32], significant advances have been made in our understanding of Ras dimers
Ras dimer formation has been recognized as a key step in the activation of Raf [65,81,98,219] and potentially other effectors [33]

Summary

Introduction

A wide variety of cell surface receptors, such as growth factor receptors [3], integrins [4], G-protein coupled receptors [5], and immune receptors [6,7] can signal to. Depending on the upstream input and the cellular context, activated Ras can recruit specific subsets of effectors and execute appropriate cellular programs . Through these effector pathways, Ras controls most aspects of cell physiology: growth, proliferation, apoptosis, metabolism, motility, to name a few [1]

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