Signal transduction and physiological roles of the small GTPase Rho and Rho effectors

2000 ◽  
Vol 28 (5) ◽  
pp. A137-A137
Author(s):  
S. Narumiya
Keyword(s):  
Signal Transduction ◽  
Small Gtpase ◽  
Rho Effectors

scholarly journals Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1264
Author(s):  
Yuxing Huang ◽  
Xin Yi ◽  
Chenlu Kang ◽  
Congying Wu
Keyword(s):  
Signal Transduction ◽  
Cell Motility ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Protein Abundance ◽  
Rhoa Activity ◽  
Cytoskeletal Dynamics ◽  
Active Pool ◽  
Spatiotemporal Control

Small GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components’ feedback to upstream signaling factors remains largely elusive. Here, we report an intriguing finding that disruption of the Arp2/3-branched actin specifically reduces RhoA activity but upregulates its total protein abundance. We further dissect the mechanisms underlying these circumstances and identify the altered cortactin/p190RhoGAP interaction and weakened CCM2/Smurf1 binding to be involved in GTP-RhoA reduction and total RhoA increase, respectively. Moreover, we find that cytokinesis defects induced by Arp2/3 inhibition can be rescued by activating RhoA. Our study reveals an intricate feedback from the actin cytoskeleton to the small GTPase. Our work highlights the role of Arp2/3-branched actin in signal transduction aside from its function in serving as critical cytoskeletal components to maintain cell morphology and motility.

The Suppression of Small GTPase Rho Signal Transduction Pathway Inhibits Angiogenesis in Vitro and in Vivo

2000 ◽  
Vol 269 (2) ◽  
pp. 633-640 ◽  
Author(s):  
Shigeki Uchida ◽  
Go Watanabe ◽  
Yutaka Shimada ◽  
Masato Maeda ◽  
Atsushi Kawabe ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Small Gtpase ◽  
Transduction Pathway

scholarly journals Rho and Anillin-dependent Control of mDia2 Localization and Function in Cytokinesis

2010 ◽  
Vol 21 (18) ◽  
pp. 3193-3204 ◽  
Author(s):  
Sadanori Watanabe ◽  
Katsuya Okawa ◽  
Takashi Miki ◽  
Satoko Sakamoto ◽  
Tomoko Morinaga ◽  
...  
Keyword(s):  
Rna Interference ◽  
Rho Gtpase ◽  
Small Gtpase ◽  
Cleavage Furrow ◽  
3T3 Cells ◽  
Actin Nucleation ◽  
Inhibitory Domain ◽  
And Function ◽  
Rho Effectors ◽  
Nih 3T3

Diaphanous-related formin, mDia, is an actin nucleation/polymerization factor functioning downstream of the small GTPase Rho. Although Rho is critically involved in cytokinesis, it remains elusive how Rho effectors and other regulators of cytoskeletons work together to accomplish this process. Here we focused on mDia2, an mDia isoform involved in cytokinesis of NIH 3T3 cells, and analyzed mechanisms of its localization in cytokinesis. We found that targeting of mDia2 to the cleavage furrow requires not only its binding to RhoA but also its diaphanous-inhibitory domain (DID). We then performed pulldown assays using a fragment containing the latter domain as a bait and identified anillin as a novel mDia2 interaction partner. The anillin-binding is competitive with the diaphanous autoregulatory domain (DAD) of mDia2 in its autoinhibitory interaction. A series of RNA interference and functional rescue experiments has revealed that, in addition to the Rho GTPase-mediated activation, the interaction between mDia2 and anillin is required for the localization and function of mDia2 in cytokinesis.

scholarly journals Photolysis of caged sphingosine-1-phosphate induces barrier enhancement and intracellular activation of lung endothelial cell signaling pathways

2011 ◽  
Vol 300 (6) ◽  
pp. L840-L850 ◽  
Author(s):  
Peter V. Usatyuk ◽  
Donghong He ◽  
Vytas Bindokas ◽  
Irina A. Gorshkova ◽  
Evgeny V. Berdyshev ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Adherens Junction ◽  
Small Gtpase ◽  
Cell Periphery ◽  
Cellular Functions ◽  
S1p Receptors ◽  
Sphingosine 1 Phosphate ◽  
Lung Endothelial Cells ◽  
Barrier Regulation

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that mediates cellular functions by ligation via G protein-coupled S1P receptors. In addition to its extracellular action, S1P also has intracellular effects; however, the signaling pathways modulated by intracellular S1P remain poorly defined. We have previously demonstrated a novel pathway of intracellular S1P generation in human lung endothelial cells (ECs). In the present study, we examined the role of intracellular S1P generated by photolysis of caged S1P on EC barrier regulation and signal transduction. Intracellular S1P released from caged S1P caused mobilization of intracellular calcium, induced activation of MAPKs, redistributed cortactin, vascular endothelial cadherin, and β-catenin to cell periphery, and tightened endothelial barrier in human pulmonary artery ECs. Treatment of cells with pertussis toxin (PTx) had no effect on caged S1P-mediated effects on Ca2+ mobilization, reorganization of cytoskeleton, cell adherens junction proteins, and barrier enhancement; however, extracellular S1P effects were significantly attenuated by PTx. Additionally, intracellular S1P also activated small GTPase Rac1 and its effector Ras GTPase-activating-like protein IQGAP1, suggesting involvement of these proteins in the S1P-mediated changes in cell-to-cell adhesion contacts. Downregulation of sphingosine kinase 1 (SphK1), but not SphK2, with siRNA or inhibition of SphK activity with an inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole (CII) attenuated exogenously administrated S1P-induced EC permeability. Furthermore, S1P1 receptor inhibitor SB649164 abolished exogenous S1P-induced transendothelial resistance changes but had no effect on intracellular S1P generated by photolysis of caged S1P. These results provide evidence that intracellular S1P modulates signal transduction in lung ECs via signaling pathway(s) independent of S1P receptors.

Sign in / Sign up

Export Citation Format

Share Document