Characterization of putative regulators of the small GTPase, Rac, in Drosophila

The Rho s ubfamily G TPases (Rho, R ac, C dc42) are small G TP-binding proteins that act as switches, controlling many cellular functions.These GTPases fluctuate between a GTP-bound 'on' state and a GDP-bound 'off state, this being catalyzed by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPS).Rac, a possible oncogene, has diverse roles including regulation of cell adhesion, the release of arachidonic acid, formation of F-actin based membrane ruffles/lamellipodia, assembly of multi-molecular focal complexes, apoptosis, and regulation of the JNK MAP kinase pathway.Model systems such as Drosophila have furthered the understanding of the functional roles of Rac in neuronal development, epithelial morphogenesis, and apoptosis.The use of model systems allows the study of molecular processes at levels not possible in cell culture.These include genetic approaches and the study of gene function at the level of tissue morphogenesis.Three putative interactors of Rac, originally identified in mammals, were studied in Drosophila.Sra-1, a cytoskeletal effector, was found to interact with Rac and had roles in neuronal development and F-actin regulation.POSH, a modulator of JNK signaling in mammals, was found to indirectly modulate Rac in Drosophila but was not required for JNK signaling during embryonic development.Drosophila POSH also had a role in apoptosis during development.RhoGAP68F, a GAP protein, was found to preferentially negatively regulate activated Rho rather than Rac in Drosophila and was therefore not investigated further.