Alternative titles; symbols
HGNC Approved Gene Symbol: RND2
Cytogenetic location: 17q21.31 Genomic coordinates (GRCh38): 17:43,025,231-43,032,041 (from NCBI)
Rho family GTPases, such as RhoA (165390), are involved in reorganization of the actin cytoskeleton and subsequent morphologic changes in various cell types. RND2 stimulates RhoA activity (Tanaka et al., 2006).
In the course of a complete genomic sequence analysis of 117 kb from chromosome 17 containing the BRCA1 gene (113705) located on 17q21, Smith et al. (1996) identified just centromeric to the BRCA1 gene a novel gene they designated RHO7. RHO7 was identified initially as a homolog to the RHO family (see 165370) of GTP-binding proteins (Chardin, 1991) by a database search using deduced amino acid sequences from predicted exons. The gene was found to be highly similar to the mouse EST homolog, with more than 90% identity between the 2 nucleotide sequences.
By screening a human fetal brain cDNA library using bovine Rnd1 (609038) as probe, Nobes et al. (1998) cloned RND2. The deduced protein contains 227 amino acids and has a calculated molecular mass of 25.3 kD. It has 3 guanine-binding motifs, 2 loops and a threonine involved in phosphate binding, and 3 major residues that coordinate magnesium in the GTP-bound state. However, RND2 lacks the residues important for the intrinsic GTPase activity of RAS (see 190020). RND2 ends with a CAAX box motif and a terminal methionine residue, suggesting that RND2 is farnesylated. Northern blot analysis detected high expression of a 1.5-kb RND2 transcript only in testis, with little to no expression in all other adult and fetal tissues examined.
Using yeast 2-hybrid analysis, Tanaka et al. (2006) identified rat Prag1 (617344) as an Rnd2-binding protein. Coimmunoprecipitation studies showed that the Prag1 C terminus bound Rnd2 in transfected HEK293T cells and endogenously in embryonic rat brain. Cotransfection of Prag1 with Rnd2 caused cell contraction that was inhibited by a dominant-negative form of RhoA (165390) or by Rho-kinase inhibitors, suggesting that Prag1 acts through the RhoA/Rho-kinase signaling pathway. Both Rnd2 and Prag1 localized to neurite tips, as well as to the cell body, in NGF (162030)-treated rat PC12 embryonic rat neural crest cells. Expression of full-length Prag1, Prag1 and Rnd2, or the N terminus of Prag1 inhibited NGF-induced neurite outgrowth in PC12 cells. Conversely, knockdown of Prag1 via short interfering RNA resulted in significantly longer neurites in NGF-treated PC12 cells. Tanaka et al. (2006) concluded that RND2 regulates neurite outgrowth by functioning as a RhoA activator through PRAG1.
Heng et al. (2008) demonstrated that the proneural protein neurogenin-2 (Neurog2; 606624), which controls neurogenesis in the embryonic cortex, directly induces the expression of the small GTP-binding protein Rnd2 in newly generated mouse cortical neurons before they initiate migration. Rnd2 silencing leads to a defect in radial migration of cortical neurons similar to that observed when the Neurog2 gene is deleted. Remarkably, restoring Rnd2 expression in Neurog2-mutant neurons is sufficient to rescue their ability to migrate. Heng et al. (2008) concluded that their results identified Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrated that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behavior of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP-binding protein.
By FISH, Nobes et al. (1998) mapped the RND2 gene to chromosome 17q21.
Chardin, P. Small GTP-binding proteins of the ras family: a conserved functional mechanism? Cancer Cells 3: 117-126, 1991. [PubMed: 1909153]
Heng, J. I.-T., Nguyen, L., Castro, D. S., Zimmer, C., Wildner, H., Armant, O., Skowronska-Krawczyk, D., Bedogni, F., Matter, J.-M., Hevner, R., Guillemot, F. Neurogenin 2 controls cortical neuron migration through regulation of Rnd2. Nature 455: 114-118, 2008. [PubMed: 18690213] [Full Text: https://doi.org/10.1038/nature07198]
Nobes, C. D., Lauritzen, I., Mattei, M.-G., Paris, S., Hall, A., Chardin, P. A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion. J. Cell Biol. 141: 187-197, 1998. [PubMed: 9531558] [Full Text: https://doi.org/10.1083/jcb.141.1.187]
Smith, T. M., Lee, M. K., Szabo, C. I., Jerome, N., McEuen, M., Taylor, M., Hood, L., King, M.-C. Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1. Genome Res. 6: 1029-1049, 1996. [PubMed: 8938427] [Full Text: https://doi.org/10.1101/gr.6.11.1029]
Tanaka, H., Katoh, H., Negishi, M. Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity. J. Biol. Chem. 281: 10355-10364, 2006. [PubMed: 16481321] [Full Text: https://doi.org/10.1074/jbc.M511314200]