Like other members of the Rho family of Ras-related GTPases it regulates the organization of the actin cytoskeleton in response to extracellular growth factors.
Regulation
Most Rho family members cycle between an inactive GDP-bound form and an active GTP-bound form. However, members of the Rnd subgroup of the Rho family are exceptions to this, binding detectably only to GTP, while having low GTPase activity, if any.[7] Instead, Rnd family proteins are regulated through other mechanisms that control their production, degradation, phosphorylation, and localization.[8]
Interactions
In its GTP-bound form, RhoA exposes regions that allow it to interact with downstream targets. Rnd3 contains a region which is similar to the one RhoA exposes for interaction with ROCK1, allowing Rnd3 to compete with RhoA for interaction with ROCK1. By binding to ROCK1, Rnd3 inhibits it from phosphorylating downstream targets necessary for stress fiber formation. Rnd3 is also directly involved in controlling RhoA activity through suppression of PLEKHG5[9] and activation of ARHGAP5.[10] Interaction with UBXD5 has also been shown.[11]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ridley AJ (October 2006). "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends in Cell Biology. 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. PMID16949823.
Bektic J, Pfeil K, Berger AP, Ramoner R, Pelzer A, Schäfer G, et al. (September 2005). "Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis". The Prostate. 64 (4): 332–40. doi:10.1002/pros.20243. PMID15754346. S2CID20256303.
Kim YS, Hori M, Yasuda K, Ozaki H (December 2005). "Differences in the gestational pattern of mRNA expression of the Rnd family in rat and human myometria". Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. 142 (4): 410–5. doi:10.1016/j.cbpa.2005.08.028. PMID16311049.
Poch E, Miñambres R, Mocholí E, Ivorra C, Pérez-Aragó A, Guerri C, et al. (February 2007). "RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line". Experimental Cell Research. 313 (4): 719–31. doi:10.1016/j.yexcr.2006.11.006. hdl:10550/94197. PMID17182035.
PDB gallery
1gwn: THE CRYSTAL STRUCTURE OF THE CORE DOMAIN OF RHOE/RND3 - A CONSTITUTIVELY ACTIVATED SMALL G PROTEIN
1m7b: Crystal structure of Rnd3/RhoE: functional implications
