RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

Abstract

SummaryRhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.

A functional siRNA screen identifies RhoGTPase-associated genes involved in thrombin-induced endothelial permeability

“…Surprisingly, the atypical GTPase RhoD appears to play a barrier-protective role. This is in line with recent data showing that RhoD stabilizes the actin cytoskeleton [ 13 ] and inhibits RhoC-ROCK-dependent cell contraction [ 60 ].…”

Salmonellaexploits host Rho GTPase signalling pathways through the phosphatase activity of SopB

“…Although RhoD was recruited to S. Typhimurium invasion sites in a SopB-dependent manner, it did not contribute to any of the tested phenotypes. RhoD has been shown to participate in actin cytoskeleton reorganisation (Blom, Reis, Heldin, Kreuger, & Aspenstrom, 2017;Durkin et al, 2017;Gad, Nehru, Ruusala, & Aspenstrom, 2012;Koizumi et al, 2012;Nehru, Almeida, & Aspenstrom, 2013) and membrane trafficking events (Blom et al, 2015;Nehru, Voytyuk, Lennartsson, & Aspenstrom, 2013). Future studies are needed to elucidate its role in S. Typhimurium infection.…”

Meeting report – Cellular dynamics: membrane–cytoskeleton interface

“…RhoD at the plasma membrane acts through the kinase PAK6 to inhibit RhoCmediated ROCK activation and the resulting cortical contraction. They now show that F11 antagonizes this process by binding to RhoD, thereby alleviating its inhibitory effect on RhoC (Durkin et al, 2017). These findings thus reveal a novel contractility mechanism that is independent of the more widely studied RhoAmediated pathway.…”