Rab Proteins and the Organization of Organelle Membrane Domains - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 16

Chapter 2
Rab Proteins and the Organization
of Organelle Membrane Domains

Marnix Wieffer, Marisa P. McShane, and Marino Zerial

Abstract Many critical cellular processes, like vesicular transport and signaling,
rely on the establishment and maintenance of membrane domains. Membrane
domains consist of a cluster of specific lipids and proteins that provide membranes
with a distinct molecular identity. Rab GTPases are one of the main coordinators of
membrane domain formation and dynamics. In this chapter, we will give a brief
introduction into Rab GTPases and focus on how they create and coordinate
membrane domains. This will include an in-depth look into the Rab effectors and
binding partners that define membrane domains. Throughout we will highlight how
these proteins are regulated such as via feedback and feed-forward loops to create
cascades. Finally, we propose that signaling domains on organelles are also coor-
dinated by Rab GTPases.

Keywords Rab GTPase • Endosome • Rab effector • Membrane domain

• Signaling

2.1 Introduction

It is becoming increasingly clear that cellular membranes are not homogeneous but
highly compartmentalized into membrane domains of different size, formed by
lipid-lipid, protein-protein, and protein-lipid interactions. Such membrane
domains are key to the formation of morphologically and functionally distinguish-
able features like vesicular coats, tubules, and signaling platforms (Gould and
Lippincott-Schwartz 2009 ; Bonifacino and Glick 2004 ). Other examples of mem-
brane nanodomains are lipid rafts and Ras nanoclusters (Lingwood and Simons
2010 ; Abankwa et al. 2008 ; Hancock and Parton 2005 ).