RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Charlotte H. Durkin, Flavia Leite, João V. Cordeiro, Yutaka Handa, Yoshiki Arakawa, Ferran Valderrama, Michael Way
RhoA-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.

Graphical abstract

Teaser

Many different viral infections induce cell contraction and blebbing. Durkin, Leite, et al. show that during vaccinia infection, RhoC and not RhoA regulates this ROCK-mediated cytopathic effect of cell contraction. They delineate a pathway for RhoC regulation, in which the viral protein F11 blocks RhoC antagonism by RhoD-recruited Pak6.


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