Trends in Cell Biology
Volume 16, Issue 10, October 2006, Pages 522-529
Journal home page for Trends in Cell Biology

Review
Special issue: Membrane Dynamics
Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking

https://doi.org/10.1016/j.tcb.2006.08.006Get rights and content

Rho GTPases are well known to regulate actin dynamics. They activate two types of actin nucleators, WASP/WAVE proteins and Diaphanous-related formins (DRFs), which induce different types of actin organization. Their ability to interact with membranes allows them to target actin polymerization to discrete sites on the plasma membrane and to intracellular membrane compartments and thereby induce membrane protrusions or regulate vesicle movement. Most studies have concentrated on just three of the 22 mammalian Rho proteins, RhoA, Rac1 and Cdc42. However, recent research indicates that several other members of the Rho family, including Rif, RhoD, TC10 and Wrch1, and also related Rho-of-plants proteins (ROPs) in plants, stimulate actin polymerization and affect plasma membrane protrusion and/or vesicular traffic.

Introduction

Rho GTPases are found in all eukaryotic organisms and regulate cell polarity and motility through their effects on the cytoskeleton, membrane trafficking and cell adhesion 1, 2. In mammals there are 22 Rho GTPases (Table 1), many of which affect cell morphology 1, 3, 4. In yeasts and plants, several Rho GTPases contribute directly to polarized cell growth by affecting the actin cytoskeleton 5, 6, 7.

Most Rho GTPases act on membranes and affect the movement of these membranes by changing the membrane-associated actin cytoskeleton. The best-studied members of the family are RhoA, Rac1 and Cdc42, and in mammalian cells Rac1 and Cdc42 have long been known to induce plasma membrane protrusions known as lamellipodia and filopodia by stimulating actin polymerization. Other Rho GTPases, including RhoG, RhoD, TC10 and Rif (also called RhoF), can also induce actin-based protrusions at the plasma membrane 3, 8, 9. On the other hand, several Rho GTPases, including RhoA, RhoB, RhoD and Cdc42, affect specific steps of vesicle trafficking between different intracellular compartments, for example exocytosis or Golgi-to-endoplasmic reticulum (ER) transport and, as with plasma membrane protrusion, their ability to induce actin polymerization is important for these activities 10, 11.

Here, I discuss the regulation and localization of Rho GTPases, how they induce different types of actin filament organization and how this in turn affects both plasma membrane protrusion and vesicle trafficking.

Section snippets

Regulation and localization of Rho GTPases

Most Rho family proteins can bind to GTP and GDP and have intrinsic GTPase activity. In their GTP-bound conformation they interact with and activate downstream target proteins. Their activity is regulated by guanine nucleotide exchange factors (GEFs), which stimulate release of GDP, allowing GTP to bind. They are down-regulated by GTPase-activated proteins (GAPs), which catalyse GTP hydrolysis, converting the proteins to the GDP-bound inactive conformation. Exceptions are Rnd1, Rnd2, Rnd3 (also

Rho GTPases and actin polymerization

Rho GTPases activate two different kinds of molecules that directly stimulate actin polymerization, WASP/WAVE proteins and Diaphanous-related formins (DRFs; Box 2). Although RhoA, Rac1 and Cdc42 have been most studied for their effects on these proteins, other Rho GTPases interact with DRFs (Table 2). WASP/WAVE proteins induce actin polymerization via the Arp2/3 complex, which stimulates the formation of a new actin filament branching off an existing filament (Box 2) [26]. Cdc42 binds directly

Rho GTPases and plasma membrane dynamics

Rho GTPases are believed to stimulate plasma membrane protrusion by inducing actin filament nucleation and polymerization on or close to membranes. This process has been studied extensively in vitro using beads or membrane vesicles with portions of actin-nucleating proteins attached [26].

Rho GTPases and vesicle trafficking

Several Rho GTPases localize to specific intracellular membrane compartments in addition to or instead of the plasma membrane (Table 1), and for some of these there is good evidence that their principal site of action is likely to be on these compartments.

Rho GTPases and polarized membrane growth in plants

Studies on Rho homologues in plants have provided new insight into the links between the actin cytoskeleton and membrane dynamics. Plants have Rho-related proteins known as ROPs (Rho-of-plants) or RACs, several of which affect membrane trafficking 5, 6. Plants have homologues of mammalian Rho targets including WAVEs, formins, phospholipase D and NADPH oxidase, although it is not clear whether plant formins interact with ROPs [92]. In Arabidopsis, constitutively active AtRAC10 induces

Conclusions and future perspectives

By stimulating actin dynamics, Rho GTPases induce plasma membrane protrusion and regulate vesicle trafficking. The two types of Rho-regulated actin nucleators, WASPs/WAVEs and DRFs, induce a branching actin filament network or parallel filaments, respectively, and thus contribute to different types of membrane protrusion: WAVEs (but probably not WASPs) to lamellipodia and DRFs to filopodia. WASPs and DRFs also seem to have distinct roles in vesicle trafficking: WASPs facilitate membrane

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