NCBI Summary:
The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
Rac and Arp2/3-Nucleated Actin Networks Antagonize Rho During Mitotic and Meiotic Cleavages. Pal D et al. (2020) In motile cells, the activities of the different Rho family GTPases are spatially segregated within the cell, and during cytokinesis there is evidence that this may also be the case. But while Rho's role as the central organizer for contractile ring assembly is well established, the role of Rac and the branched actin networks it promotes is less well understood. To characterize the contributions of these proteins during cytokinesis, we manipulated Rac and Arp2/3 activity during mitosis and meiosis in sea urchin embryos and sea star oocytes. While neither Rac nor Arp2/3 were essential for early embryonic divisions, loss of either Rac or Arp2/3 activity resulted in polar body defects. Expression of activated Rac resulted in cytokinesis failure as early as the first division, and in oocytes, activated Rac suppressed both the Rho wave that traverses the oocyte prior to polar body extrusion as well as polar body formation itself. However, the inhibitory effect of Rac on cytokinesis, polar body formation and the Rho wave could be suppressed by effector-binding mutations or direct inhibition of Arp2/3. Together, these results suggest that Rac- and Arp2/3 mediated actin networks may directly antagonize Rho signaling, thus providing a potential mechanism to explain why Arp2/3-nucleated branched actin networks must be suppressed at the cell equator for successful cytokinesis.//////////////////Effects of RAC1 on Proliferation of Hen Ovarian Prehierarchical Follicle Granulosa Cells. Tyasi TL et al. (2020) RAC1 belongs to the small G protein Rho subfamily and is implicated in regulating gene expression, cell proliferation and differentiation in mammals and humans; nevertheless, the function of RAC1 in growth and development of hen ovarian follicles is still unclear. This study sought to understand the biological effects of RAC1 on granulosa cell (GC) proliferation and differentiation of hen ovarian prehierarchical follicles. Firstly, our results showed expression levels of RAC1 mRNA in the follicles with diameters of 7.0-8.0 mm, 6.0-6.9 mm and 1.0-3.9 mm were greater than other follicles (p < 0.05). The RAC1 protein was mainly expressed in oocyte and its around GCs and stromal tissues of the prehierarchical follicles by immunohistochemistry. Further investigation revealed the RAC1 gene remarkably enhanced the mRNA and protein expression levels of FSHR (a marker of follicle selection), CCND2 (a marker of cell-cycle progression and GC differentiation), PCNA (a marker of GC proliferation), StAR and CYP11A1 (markers of GC differentiation and steroidogenesis) (p < 0.05). Furthermore, our data demonstrated siRNA interference of RAC1 significantly reduced GC proliferation (p < 0.05), while RAC1 gene overexpression enhanced GC proliferation in vitro (p < 0.05). Collectively, this study provided new evidence that the biological effects of RAC1 on GC proliferation, differentiation and steroidogenesis of chicken ovary follicles.////////////////// Rac1 is dispensable for oocyte maturation and female fertility in vivo. Hao JX et al. (2017) Oocyte maturation, the important process to produce female haploid gamete, accompanies with polarity establishment and highly asymmetric cell division to emit minor polar body within little cytoplasm. Microfilaments play central roles in polarity establishment and asymmetric cell division. Several actin regulators like WASP protein family as well as small GTPases function in microfilament dynamics, involving the process. Rac1, one member of RhoGTPases, has been reported to regulate the polarity and asymmetric cell division in mouse oocytes in vitro. The physiological role of Rac1 in mouse oocyte remains unknown. By conditional knockout technology, we specifically deleted Rac1 gene in mouse oocyte, and found that Rac1 deletion exerted little effect on mouse oocyte maturation including polarity establishment and asymmetric division, and the mutant mice showed normal fertility.//////////////////
Rac activity is polarized and regulates meiotic spindle stability and anchoring in Mammalian oocytes. Halet G et al. Mammalian meiotic divisions are asymmetrical and generate a large oocyte and two small polar bodies. This asymmetry results from the anchoring of the meiotic spindle to the oocyte cortex and subsequent cortical reorganization, but the mechanisms involved are poorly understood. We investigated the role of Rac in oocyte meiosis by using a fluorescent reporter for Rac-GTP. We find that Rac-GTP is polarized in the cortex overlying the meiotic spindle. Polarization of Rac activation occurs during spindle migration and is promoted by the proximity of chromatin to the cortex. Inhibition of Rac during oocyte maturation caused a permanent block at prometaphase I and spindle elongation. In metaphase II-arrested oocytes, Rac inhibition caused the spindle to detach from the cortex and prevented polar body emission after activation. These results demonstrate that Rac-GTP plays a major role in oocyte meiosis, via the regulation of spindle stability and anchoring to the cortex.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa, Luteal cells
Comment
Follicular Fluid High-Density Lipoprotein (FF-HDL)-Associated Sphingosine 1-Phosphate (S1P) Promotes Human Granulosa Lutein Cell Migration via S1P Receptor Type 3 (S1PR3) and Small G Protein RAC1. Becker S et al. Coordinated migration and progesterone production by granulosa cells is critical to the development of corpus luteum, but the underlying mechanisms remain obscure. Sphingosine 1-phospate (S1P) associated with follicular fluid high-density lipoproteins (FF-HDL) was previously demonstrated to regulate ovarian angiogenesis. We here examined the effects of S1P and FF-HDL on the function of granulosa lutein cells. Both FF-HDL and S1P induced migration of primary human granulosa lutein cells (hGCs) and granulosa lutein cell line, HGL5. In addition, FF-HDL but not S1P promoted progesterone synthesis, and neither of two compounds stimulated proliferation of granulosa lutein cells. PCR and Western blot experiments demonstrated expression of S1P receptors type 1, 2, 3 and 5 but not type 4 in hGCs and HGL5 cells. FF-HDL- and S1P-induced granulosa lutein cell migration was emulated by FTY720, an agonist of S1P receptors 1, 3, 4, and 5 and by VPC24191, an agonist of S1P receptors 1 and 3, but not by SEW2871 and phytosphingosine-1-phosphate, agonists of S1P receptors 1 and 4, respectively. In addition, blockade of S1P receptor 3 with CAY1044, suramine or pertussis toxin inhibited hGCs and HGL5 cell migration towards FF-HDL or S1P, while blockade of S1P receptors 1 and 2 with W146 and JTE013, respectively, remained without effect. Both FF-HDL and S1P triggered activation of the small G protein RAC1 and the actin polymerization in granulosa cells and RAC1 inhibition with C. difficile toxin B or NSC23766 abolished FF-HDL- and S1P-induced migration. FF-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of corpus luteum.