RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.

Area of Science:

• Cell Biology
• Virology
• Molecular Biology

Background:

• RhoA-mediated myosin-II activity regulates cell contraction and blebbing in cellular processes and viral infections.
• Cell contraction and blebbing are key cytopathic effects observed in various viral infections.

Purpose of the Study:

• To investigate the role of vaccinia virus protein F11 in regulating cell contraction and blebbing.
• To elucidate the specific Rho signaling pathways involved in F11-induced cellular responses.

Main Methods:

• Localization of vaccinia virus protein F11 to the plasma membrane.
• Analysis of ROCK-mediated cell contraction post-infection.
• Investigation of RhoA, RhoC, and RhoD signaling pathways and their downstream effectors (e.g., Pak6).

Main Results:

• Vaccinia virus protein F11 is required for ROCK-mediated cell contraction starting 2 hours post-infection.
• F11-induced cell contraction relies on RhoC signaling, not RhoA.
• F11 inhibits RhoD signaling, which in turn prevents Pak6 from suppressing RhoC, thereby facilitating RhoC-driven contraction.

Conclusions:

• Vaccinia virus protein F11 manipulates host cell signaling pathways to induce cell contraction and blebbing.
• The study reveals a novel mechanism where F11 utilizes RhoC signaling by inhibiting RhoD-Pak6 pathway, distinct from previously understood RhoA pathways.
• RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.