Disease relevance of Rac1

• RhoA and Rac1 gain-of-function and loss-of-function mutants had both disruption of glial cell development and secondary effects on sensory axon fasciculation [1].

High impact information on Rac1

• Indeed, expression of constitutively active forms of Rho1 or Rac1 in adult flies results in ethanol resistance similar to that observed in whir mutants [2].
• Like many cell migrations, border cell migration is inhibited by a dominant-negative form of the GTPase Rac [3].
• Normal patterns of R cell connectivity require Pak's kinase activity and binding sites for both Dock and Cdc42/Rac [4].
• Rescue of photoreceptor degeneration in rhodopsin-null Drosophila mutants by activated Rac1 [5].
• Cell biology. Actin' up with Rac1 [6].

Biological context of Rac1

• Eye-directed expression of cdi strongly suppressed the phenotypes induced by either RacGAP(84C) gain-of-function or by the dominant negative form of Rac1, Rac1N17 [7].
• We show that constitutive activation of Rac1 leads to excessive assembly of lamellipodia and precocious halting of epithelial sweeping, possibly through premature activation of contact-inhibition machinery [8].
• Distinct functions of Rac1 and Cdc42 during axon guidance and growth cone morphogenesis in Drosophila [9].
• We have previously shown that the accumulation of cytoskeletal elements initiating cell shape changes in these cells could be inhibited by expression of a dominant-negative DRacA transgene [10].
• Various in vitro and cell culture studies on the small GTPase Rac have suggested it to be a key regulator of cell adhesion, but this notion needs to be verified in the context of embryonic development [11].

Anatomical context of Rac1

• A hair begins as a single membrane outgrowth from each wing epithelial cell, and its distal orientation is determined by the restriction of outgrowth to a single distal site on the cell circumference (Wong, L., and P. Adler. 1993. J. Cell Biol. 123:209-211.). We have examined the roles of Cdc42 and Rac1 in the formation of wing hairs [12].
• CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium [13].
• Finally, though dominant negative Rac1 is able to block filopodia formation in the overexpression experiments, only Rac2 is necessary for filopodia formed by hemocytes after parasitization [14].
• The Rac1-like phenotypes, and filopodia formation, could be blocked by co-expression of dominant negative Rac1 [14].
• In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP3) at the leading edge [15].

Associations of Rac1 with chemical compounds

• RacD possesses a 50 residue C-terminal extension and RacA a 400 residue C-terminal extension that contains a proline-rich region, two BTB domains and a novel C-terminal domain [16].

Physical interactions of Rac1

• The Radish protein has recently been reported to bind to Rac1 [Formstecher et al. (2005) Genome Res. 15:376-384], a small GTPase that regulates cytoskeletal rearrangement and influences neuronal and synaptic morphology [17].

Regulatory relationships of Rac1

• In the reciprocal pathway, co-expression of dominant negative Rho-kinase and constitutive active Rho1 induces a Rac1-like phenotype [14].
• We have made transgenic flies bearing dominant inhibitory (N17DRacA), and wild-type versions of the DRacA cDNA under control of an Hsp70 promoter [18].
• Here, we report that axon outgrowth defects within specific subsets of motoneurons expressing constitutively active Drosophila Rac1 largely persist even with the addition of an effector-loop mutation to Rac1 that disrupts its ability to bind to p21-activated kinase (Pak) and other Cdc42/Rac1 interactive-binding (CRIB)-motif effector proteins [19].
• Similar genetic evidence indicates that RacGAP50C inhibits Rac during cytokinesis [20].
• The observed genetic interactions are consistent with a model in which Rac signaling is activated by Ras and negatively regulated by RnRacGAP during spermatid differentiation [21].

Other interactions of Rac1

• Cdc42 and Rac1 are members of the rho family of small guanosinetriphosphatases and are required for a diverse set of cytoskeleton-membrane interactions in different cell types [13].
• These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect [22].
• To further elucidate this interaction we examined the activities of Rac1 and Rho1 in Drosophila cellular immune surveillance cells [14].
• These results are consistent with Cdi being a specific downstream target of Rac1 [7].
• Conversely, blocking Rac activity, either by loss-of-function mutations or expression of dominant negative Rac1, disables the assembly of both actin cable and protrusions by epithelial cells [8].

References