Arhgef25, also known as p63RhoGEF and GEFT, encodes Rho guanine nucleotide exchange factors (GEFs) that are key regulators of Rho GTPases, which in turn are master regulators of the eukaryotic cytoskeleton. It is involved in pathways like Gαq-mediated signaling, where Gαq can both recruit and allosterically activate cytosolic ARHGEF25 isoforms [1]. This gene is also associated with smooth muscle regulation, as agonists coupled to GPCRs through G(αq/11) can potentially target p63RhoGEF (Arhgef25) to regulate basal blood pressure [3].

No findings from KO/CKO mouse models were present in the provided abstracts. However, in glioblastoma, miR-3189-3p can directly target p63RhoGEF (Arhgef25), inhibiting cell proliferation and migration, suggesting its potential role in tumor growth regulation [4]. Also, in the context of postoperative cognitive dysfunction, Arhgef25 was predicted as a target gene of mmu-miR-190a-3p, indicating its possible involvement in this neurocognitive disorder [2].

In summary, Arhgef25 is crucial for regulating the cytoskeleton through Rho GTPase activation and is involved in Gαq-mediated signaling. Its role in smooth muscle regulation and potential implications in diseases like glioblastoma and postoperative cognitive dysfunction highlight its significance. Although no KO/CKO mouse model findings were available, the current research hints at its importance in understanding these disease conditions.

References:

1. van Unen, Jakobus, Yin, Taofei, Wu, Yi I, Gadella, Theodorus W J, Goedhart, Joachim. 2016. Kinetics of recruitment and allosteric activation of ARHGEF25 isoforms by the heterotrimeric G-protein Gαq. In Scientific reports, 6, 36825. doi:10.1038/srep36825. https://pubmed.ncbi.nlm.nih.gov/27833100/

2. Liu, Qiang, Hou, Aisheng, Zhang, Yongyi, Ma, Yunlong, Cao, Jiangbei. 2019. MiR-190a potentially ameliorates postoperative cognitive dysfunction by regulating Tiam1. In BMC genomics, 20, 670. doi:10.1186/s12864-019-6035-0. https://pubmed.ncbi.nlm.nih.gov/31438846/

3. Momotani, Ko, Somlyo, Avril V. 2012. p63RhoGEF: a new switch for G(q)-mediated activation of smooth muscle. In Trends in cardiovascular medicine, 22, 122-7. doi:10.1016/j.tcm.2012.07.007. https://pubmed.ncbi.nlm.nih.gov/22902181/

4. Jeansonne, Duane, DeLuca, Mariacristina, Marrero, Luis, Reiss, Krzysztof, Peruzzi, Francesca. 2015. Anti-tumoral effects of miR-3189-3p in glioblastoma. In The Journal of biological chemistry, 290, 8067-80. doi:10.1074/jbc.M114.633081. https://pubmed.ncbi.nlm.nih.gov/25645911/