The actin cytoskeleton of Dictyostelium

The actin cytoskeleton of a cell is required for cell-shape changes, cell motility and chemotaxis, as well as for cytokinesis, intracellular transport processes, development and signal transduction. It is composed of actin and associated proteins. Their interactions are highly dynamic, and constant reorganization of the actin network is required for it to perform its functions. Dictyostelium has been a model system for the analysis of the actin cytoskeleton for some time now, and research in this field has contributed to a general understanding of the structure and function of cytoskeletal proteins (for reviews see Schleicher and Noegel, 1992; Noegel and Luna, 1995). Dictyostelium has several features that make it especially well suited to studies of the actin cytoskeleton. It is a unicellular amoeba that lives as a natural phagocyte and feeds on yeast and bacteria. When cells starve, development is initiated, and cells aggregate by chemotaxis in response to relayed cAMP signals. Once the amoebae have aggregated, they form a multicellular organism that in its slug form can migrate towards light and orient in a thermotactic gradient. During development, cells differentiate into spore and stalk cells and, finally, a fruiting body is constructed. In the laboratory this program is completed within 24 hours. Multicellularity requires specific cell interactions, extracellular signals and the corresponding receptors, as well as various signal transduction pathways. Dictyostelium is haploid. This facilitates isolation of mutants but makes it difficult to study essential genes. A wide spectrum of molecular genetic techniques is available, including gene inactivation by homologous recombination, gene replacement, antisense strategies, restriction-enzyme-mediated integration (REMI), transposon-tagging-like mutagenesis, and expression of GFP fusion proteins. The 34-Mb genome is carried on six chromosomes. The Dictyostelium genome project (see http://www.uni-koeln.de/dictyostelium/) should be completed by 2002; however, information on more than 90% of the genes is already available. Dictyostelium is therefore a valuable and convenient experimental system for studies of the role of the actin cytoskeleton in cell motility, chemotaxis, signal transduction, development and differentiation. Here, we highlight new developments in three areas: (1) cytoskeletal dynamics at leading fronts, where experiments with GFP fusion proteins provided spectacular data on chemotaxis, cell movement, phagocytosis and pinocytosis (Maniak et al., 1995; Parent et al., 1998); (2) the roles of actin and actin-binding proteins as effectors of cell signalling; (3) coordination of cellular behaviour by actin and actin-binding proteins, where the genome project aided the identification of new components that reveal additional roles for the actin cytoskeleton. Moreover, we try to give an update on components of the actin cytoskeleton and putative regulatory components, and their impact on cell biology – as taken from mutant analysis (Table 1). Structural analyses of cytoskeletal proteins have also made significant contributions; these studies, however, are beyond the scope of this Commentary.