Main description:

Animal cells present an extreme variability in their shapes in relation to their physiological properties. For instance, fibroblastic cells are tightly attached to the extra-cellular matrix and display a flattened, spindle-shaped morphology. Neuronal cells self-organize as a network through a complex branching of dendrites and a long axonal extension. Resting peripheral blood lymphocytes are poorly adhesive and maintain a spherical, smooth shape, while macroph- ages produce many pseudopodal extensions involved in the recognition of foreign molecules. In addition to the variability of the morphology of the cells that constitute different organs, many cell types also modify dynamically their morphology in response to environmental changes, leading to differential cell motility, migration, adhesion, polarity or intercellular contacts. This wide plasticity of cell morphology is promoted and maintained by the cytoskeleton, which is composed of the three interconnected actin micro filaments, tubulin microtubules and intermediate filaments networks, all capable of assembly and disassembly.
Over the past few years, the Rho family of Ras-like GTPases emerged as key proteins that mediate extracellular signalling pathways leading to the forma- tion of polymerized actin-containing structures such as ruffles, lamellipodia and filopodia. Since the discovery of the first member RhoA in 1985, 13 mem- bers have so far been characterized in human cells. Most of Rho proteins are highly conserved between species as distant as yeast, slime mold, insects and mammals, which points to their fundamental role in cellular physiology.

Contents:

Rho Family Proteins and Regulation of the Actin Cytoskeleton.- 1 Introduction.- 2 Structure and Regulation of Rho Family Proteins.- 2.1 Primary Structure of Rho Family Proteins.- 2.2 Expression of Rho Family Proteins.- 2.3 Post-Translational Modifications.- 2.4 Structural Analysis of Rho Family Proteins.- 3 Rho Family Proteins and Growth Factor-Induced Actin Reorganization.- 3.1 Rho.- 3.2 Rac.- 3.3 Cdc42.- 3.4 Other Rho Family Proteins.- 3.5 Links Between Different Rho Family Proteins:A Role in Cell Migration?.- 4 Rho Family Proteins and Cell Adhesion.- 4.1 Adhesion to the Extracellular Matrix.- 4.2 Intercellular Adhesions.- 5 Rho Family Proteins and Cytokinesis.- 6 Other Responses Regulated by Rho Family Proteins.- 6.1 Activation of the NADPH Oxidase and Phagocytosis.- 6.2 Secretion and Endocytosis.- 6.3 Mitogenesis and Transformation.- 7 Conclusions.- References.- Regulation of Cytoskeleton and Cell Adhesion by Rho Targets.- 1 Introduction.- 2 Regulation of Rho Activity.- 3 Functions of Rho.- 3.1 Formation of Stress Fiber and Focal Adhesion.- 3.2 Smooth Muscle Contraction.- 3.3 Neurite Retraction.- 3.4 Cytokinesis.- 3.5 Cell-Cell Adhesion.- 3.6 Actin Filaments Beneath Plasma Membrane.- 3.7 Other Functions.- 4 Rho Targets.- 5 Functions of Rho Targets.- 5.1 Rho-Kinase and MBS.- 5.2 mDia and Bnil.- 5.3 Other Rho Targets.- 6 Conclusion.- References.- Rnd Proteins: A New Family of Rho-Related Proteins That Interfere with the Assembly of Filamentous Actin Structures and Cell Adhesion.- 1 Introduction.- 2 Characterisation of Three New Members of the Rho Family.- 3 Biochemical Properties of Rndl: G-Proteins That Do Not Switch?.- 4 Expression in Tissues and Localization of Rndl in the Brain.- 5 Effects of Rndl Expression on the Formation of Actin Stress Fibers.- 6 Localization of Rndl in Swiss 3T3 Fibroblasts and Microinjected MDCK Cells.- 7 A Role for Rnd Proteins in Transformation?.- 8 Rnd Proteins and Targets of Farnesyl-Transferase Inhibitors.- 9 Conclusions.- References.- The DH Protein Family, Exchange Factors for Rho-Like GTPases.- 1 Introduction.- 1.1 Small GTPases.- 1.2 Rho-Like GTPases.- 2 Identification of DH Proteins, GEFs for Rho-Like GTPases.- 3 Structure and Function of DH Proteins.- 3.1 Catalytic Function.- 3.2 Functional Domains in DH Proteins.- 3.2.1 DH and PH Domains.- 3.2.2 Other Domains in DH Proteins.- 4 Cellular Functions of DH Proteins.- 4.1 Oncogenic Transformation.- 4.2 Invasion.- 4.3 Neuronal Development.- 4.4 Development.- 4.5 Modulation of RasGEF Activity.- 5 DH Proteins in Signaling Pathways.- 5.1 Activation of GEF Activity by Phosphorylation.- 5.2 Activation of Rho-like GTPases by Membrane Localization of GEFs.- 5.3 Signal Mediation by DH Proteins in Protein Complexes.- 5.4 Role of DH Proteins in Ras Transformation.- 6 Concluding Remarks.- References.- RhoGAPs and RhoGDIs (His)stories of Two Families.- 1 RhoGDI (GDP Dissociation Inhibitors): Who Needs Them?.- 1.1 A Family of RhoGDIs.- 1.2 Biochemical Properties.- 1.3 From Structure to Function: Insights Deduced from RhoGDI-1 3-D Structure.- 1.4 In Vivo Functional RhoGDI as a Specific Tool for Gaining Insight into Rho Function.- 1.5 Cellular Localisation.- 1.6 A Hematopoietic RhoGDI, RhoGDI-2 (Ly/D4-RhoGDI) Could Play a Role During Apoptosis.- 1.7 A Third RhoGDI Exhibits Catalytic Specificity and Cytoskeleton Localisation.- 2 GTPase Activating Proteins (GAPs) for Rho-Like GTPases: A Catalytic Module Found Within a Plethora of Multifunctional Proteins.- 2.1 GAP Activity and Identification of p50-RhoGAP.- 2.2 Birth of the Rho-GAP Family of Proteins.- 2.3 Bcr (Breakpoint Cluster Region) Gene Product.- 2.4 Abr (Active Bcr-Related) Gene Product.- 2.5 The Chimaerin Family of Proteins (?l, ?2, ?1, and ?2).- 2.6 p85? and p85? Subunits of PI3-Kinase.- 2.7 p190 (p120-RasGAP-Associated Protein) and p190b.- 2.8 Other Mammalian Rho-GAPs: 3BP-1, RLIP76, Myr5, Myosin-IXb, p122-Arp, p115 and p58-Mgc.- 2.9 Non-Mammalian Rho-GAPs: Graf, RotundRacGAP, CeGAP, DdRacGAP, Bem2, Bem3, Dbml, LRG1 and RGA1.- 3 Conclusions.- 3.1 Too Many Rho GTPase-Regulating Factors?.- 3.2 A Final Word.- References.- Roles of PAK Family Kinases.- 1 Introduction.- 2 Distribution of PAK Family Kinases.- 3 Regulation of PAK Activity.- 4 Functions of Fungal Ste20p/PAK-Like Kinases.- 5 PAKs and Phosphorylation Pathways.- 6 PAK and Cellular Transformation.- 7 Morphological Roles for PAK Downstream of Cdc42 and Rac.- 8 Activities Associated with the Various Domains of PAK.- 8.1 Proline-Rich Domains.- 8.2 The p21-Binding Domain.- 8.3 The Auto-Regulatory Domain.- 8.4 The Kinase Domain.- 9 Conclusions.- References.- Rac and Cdc42 Effectors.- 1 Introduction.- 2 Effector Proteins of Rac and Cdc42.- 2.1 Potential Effectors of Rac and Cdc42 Involved in Cytoskeletal Rearrangements.- 2.2 Potential Effectors of Rac and Cdc42 Induced Transcriptional Activation.- 2.3 Potential Effector Pathways of Rac and Cdc42 Involved in Cell Growth Control.- 2.4 Phox 67, a Rac Target in the Superoxide Formation of Phagocytic Cells.- 3 Concluding Remarks.- References.- Small GTPases of the Rho Family and Cell Transformation.- 1 Introduction.- 1.1 The Rho Family.- 1.2 Regulators of the Rho Family and their Oncogenic Properties.- 2 Rho Proteins and Cell Transformation.- 2.1 Intrinsic Transforming Properties of Rho Proteins.- 2.2 Cross-Talk Between Rho Controlled Pathways.- 3 Cross-Talk Between Ras and Rho-Dependent Pathways in Cell Transformation.- 3.1 Cooperation Between Ras and Rho Pathways.- 3.2 Cooperation Between Raf and Rho Pathways.- 4 Signalling Pathways Downstream of Rho Proteins Involved in Cell Transformation.- 4.1 Rho-Dependent Activation of the JNK/SAPK Pathway.- 4.2 The Cytoskeleton and Rho Proteins.- 5 Rho Proteins and Apoptosis.- 6 Concluding Remarks.- References.- Rho GTP-Binding Proteins as Targets for Microbial Pathogens.- 1 Introduction.- 2 Microbial Pathogens and the Epithelial Cell Actin Cytoskeleton.- 2.1 Microbial Pathogens and Actin.- 2.2 Rho GTP-Binding Proteins.- 3 Interaction of Bacterial Protein Toxins with the Rho Subfamily of GTP-Binding Proteins.- 3.1 Toxins Inhibiting Rho.- 3.2 Toxins Activating Rho.- 4 Invasive Bacterial Factors and the Rho Subfamily of GTP-Binding Proteins.- 4.1 Bacterial Effectors of Salmonella or Shigella-Induced Internalization by Epithelial Cells.- 4.2 Cdc42 Is Involved in Salmonella Entry, Whereas Rho Proteins Are Required for Shigella Entry.- References.- Rho GTPases in Development.- 1 Introduction.- 2 The Rho Family of Small GTPases.- 2.1 Rho-Mediated Signal Transduction.- 2.2 Genetic Analysis of Signal Transduction in Simple Organisms.- 3 Genetic Analysis of Rho GTPases in Drosophila Development.- 3.1 Expression of Rho Family GTPases in Drosophila Embryogenesis.- 3.2 Oogenesis.- 3.3 Gastrulation.- 3.4 Dorsal Closure.- 3.5 Tissue Polarity.- 3.6 Eye Development.- 3.7 Neural Development.- 3.8 Muscle Development.- 4 Rho Family GTPases in C. elegans.- 4.1 Conservation of Rho GTPases and their Regulators and Targets in Worms.- 4.2 Embryo Elongation.- 4.3 Neural Development.- 5 Rho GTPase Function in Mammals.- 5.1 Knockout Mice.- 5.2 Transgenic Mice.- 5.3 Diseases of Human Development.- 6 Summary.- References.- Erratum.