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The internal structure of a cell can be affected by signals in the form of small molecules outside the cell. These changes can then alter the shape or adhesiveness of the cell. This volume centers particularly on one family of cellular proteins which transmit these signals, the Rho Ras-like GTPases, and examines their role in normal cellular processes and development. Also discussed are their roles in cancer formation and microbial pathogenesis.
This volume summarizes the current understanding of the Rho family of signal transduction molecules
Texte du rabat
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.
Contenu
Rho Family Proteins and Regulation of the Actin Cytoskeleton.- 1 Introduction.- 2 Structure and Regulation of Rho Family Proteins.- 3 Rho Family Proteins and Growth Factor-Induced Actin Reorganization.- 4 Rho Family Proteins and Cell Adhesion.- 5 Rho Family Proteins and Cytokinesis.- 6 Other Responses Regulated by Rho Family Proteins.- 7 Conclusions.- References.- Regulation of Cytoskeleton and Cell Adhesion by Rho Targets.- 1 Introduction.- 2 Regulation of Rho Activity.- 3 Functions of Rho.- 4 Rho Targets.- 5 Functions of 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.- 2 Identification of DH Proteins, GEFs for Rho-Like GTPases.- 3 Structure and Function of DH Proteins.- 4 Cellular Functions of DH Proteins.- 5 DH Proteins in Signaling Pathways.- 6 Concluding Remarks.- References.- RhoGAPs and RhoGDIs (His)stories of Two Families.- 1 RhoGDI (GDP Dissociation Inhibitors): Who Needs Them?.- 2 GTPase Activating Proteins (GAPs) for Rho-Like GTPases: A Catalytic Module Found Within a Plethora of Multifunctional Proteins.- 3 Conclusions.- References.- Roles of PAK Family Kinases.- 1Introduction.- 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.- 9 Conclusions.- References.- Rac and Cdc42 Effectors.- 1 Introduction.- 2 Effector Proteins of Rac and Cdc42.- 3 Concluding Remarks.- References.- Small GTPases of the Rho Family and Cell Transformation.- 1 Introduction.- 2 Rho Proteins and Cell Transformation.- 3 Cross-Talk Between Ras and Rho-Dependent Pathways in Cell Transformation.- 4 Signalling Pathways Downstream of Rho Proteins Involved in Cell Transformation.- 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.- 3 Interaction of Bacterial Protein Toxins with the Rho Subfamily of GTP-Binding Proteins.- 4 Invasive Bacterial Factors and the Rho Subfamily of GTP-Binding Proteins.- References.- Rho GTPases in Development.- 1 Introduction.- 2 The Rho Family of Small GTPases.- 3 Genetic Analysis of Rho GTPases in Drosophila Development.- 4 Rho Family GTPases in C. elegans.- 5 Rho GTPase Function in Mammals.- 6 Summary.- References.- Erratum.