Rnd3 Explained

Rnd3 is a small (~21 kDa) signaling G protein (to be specific, a GTPase), and is a member of the Rnd subgroup of the Rho family of GTPases.^[1] It is encoded by the gene RND3.^[2]

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.^[3] Instead, Rnd family proteins are regulated through other mechanisms that control their production, degradation, phosphorylation, and localization.^[4]

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^[5] and activation of ARHGAP5.^[6] Interaction with UBXD5 has also been shown.^[7]

Further reading

• Foster R, Hu KQ, Lu Y, Nolan KM, Thissen J, Settleman J . Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation . Molecular and Cellular Biology . 16 . 6 . 2689–99 . June 1996 . 8649376 . 231259 . 10.1128/MCB.16.6.2689 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Nobes CD, Lauritzen I, Mattei MG, 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 . The Journal of Cell Biology . 141 . 1 . 187–97 . April 1998 . 9531558 . 2132722 . 10.1083/jcb.141.1.187 .
• Katoh H, Harada A, Mori K, Negishi M . Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers . Molecular and Cellular Biology . 22 . 9 . 2952–64 . May 2002 . 11940653 . 133765 . 10.1128/MCB.22.9.2952-2964.2002 .
• Fiegen D, Blumenstein L, Stege P, Vetter IR, Ahmadian MR . Crystal structure of Rnd3/RhoE: functional implications . FEBS Letters . 525 . 1–3 . 100–4 . August 2002 . 12163169 . 10.1016/S0014-5793(02)03094-6 . 24691079 . free .
• Riento K, Guasch RM, Garg R, Jin B, Ridley AJ . RhoE binds to ROCK I and inhibits downstream signaling . Molecular and Cellular Biology . 23 . 12 . 4219–29 . June 2003 . 12773565 . 156133 . 10.1128/MCB.23.12.4219-4229.2003 .
• Wennerberg K, Forget MA, Ellerbroek SM, Arthur WT, Burridge K, Settleman J, Der CJ, Hansen SH . Rnd proteins function as RhoA antagonists by activating p190 RhoGAP . Current Biology . 13 . 13 . 1106–15 . July 2003 . 12842009 . 6918695 . 10.1016/S0960-9822(03)00418-4 . 2003CBio...13.1106W .
• Bektic J, Pfeil K, Berger AP, Ramoner R, Pelzer A, Schäfer G, Kofler K, Bartsch G, Klocker H . Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis . The Prostate . 64 . 4 . 332–40 . September 2005 . 15754346 . 10.1002/pros.20243 . 20256303 .
• Rubenstein NM, Chan JF, Kim JY, Hansen SH, Firestone GL . Rnd3/RhoE induces tight junction formation in mammary epithelial tumor cells . Experimental Cell Research . 305 . 1 . 74–82 . April 2005 . 15777789 . 10.1016/j.yexcr.2004.12.010 .
• Benzinger A, Muster N, Koch HB, Yates JR, Hermeking H . Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer . Molecular & Cellular Proteomics . 4 . 6 . 785–95 . June 2005 . 15778465 . 10.1074/mcp.M500021-MCP200 . free .
• Kim YS, Hori M, Yasuda K, Ozaki H . 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 . December 2005 . 16311049 . 10.1016/j.cbpa.2005.08.028 .
• Poch E, Miñambres R, Mocholí E, Ivorra C, Pérez-Aragó A, Guerri C, Pérez-Roger I, Guasch RM . 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 . February 2007 . 17182035 . 10.1016/j.yexcr.2006.11.006 . 10550/94197 . free .

Notes and References

1. Ridley AJ . Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking . Trends in Cell Biology . 16 . 10 . 522–9 . October 2006 . 16949823 . 10.1016/j.tcb.2006.08.006 .
2. Web site: Entrez Gene: RND3 Rho family GTPase 3.
3. Riento K, Guasch RM, Garg R, Jin B, Ridley AJ . RhoE binds to ROCK I and inhibits downstream signaling . Molecular and Cellular Biology . 23 . 12 . 4219–29 . June 2003 . 12773565 . 156133 . 10.1128/MCB.23.12.4219-4229.2003 .
4. Chardin P . Function and regulation of Rnd proteins . Nature Reviews. Molecular Cell Biology . 7 . 1 . 54–62 . January 2006 . 16493413 . 10.1038/nrm1788 . 90941 .
5. Goh LL, Manser E . The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin-related domain . PLOS ONE . 5 . 8 . e12409 . August 2010 . 20811643 . 2928299 . 10.1371/journal.pone.0012409 . 2010PLoSO...512409G . Toru . Ouchi . free .
6. Wennerberg K, Forget MA, Ellerbroek SM, Arthur WT, Burridge K, Settleman J, Der CJ, Hansen SH . Rnd proteins function as RhoA antagonists by activating p190 RhoGAP . Current Biology . 13 . 13 . 1106–15 . July 2003 . 12842009 . 6918695 . 10.1016/S0960-9822(03)00418-4 . 2003CBio...13.1106W .
7. Katoh H, Harada A, Mori K, Negishi M . Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers . Molecular and Cellular Biology . 22 . 9 . 2952–64 . May 2002 . 11940653 . 133765 . 10.1128/MCB.22.9.2952-2964.2002 .