Activation of Small GTPases RhoA and Rac1 Is Required for Avian Reovirus p10-induced Syncytium Formation

  • Liu, Hung-Jen (Department of Veterinary Medicine, National Pingtung University of Science and Technology) ;
  • Lin, Ping-Yuan (Graduate Institute and Department of Life Science, Tzu-Chi University) ;
  • Wang, Ling-Rung (Graduate Institute of Medical Science, Tzu-Chi University) ;
  • Hsu, Hsue-Yin (Graduate Institute and Department of Life Science, Tzu-Chi University) ;
  • Liao, Ming-Huei (Department of Veterinary Medicine, National Pingtung University of Science and Technology) ;
  • Shih, Wen-Ling (Graduate Institute and Department of Life Science, Tzu-Chi University)
  • Received : 2008.05.13
  • Accepted : 2008.07.07
  • Published : 2008.10.31

Abstract

The first ORF of the ARV S1133 S1 segment encodes the nonstructural protein p10, which is responsible for the induction of cell syncytium formation. However, p10-dependent signaling during syncytium formation is fully unknown. Here, we show that dominant negative RhoA, Rho inhibitor C3 exoenzyme, ROCK/Rho-kinase inhibitor Y-27632 and Rac1 inhibitor NSC23766 inhibit p10-mediated cell fusion. p10 over-expression is concomitant with activation and membrane translocation of RhoA and Rac1, but not cdc42. RhoA and Rac1 downstream events, including JNK phosphorylation and transcription factor AP-1 and $NF-{\kappa}B$ activation, as well as MLC expression and phosphorylation are simultaneously activated by p10. p10 point mutant T13M possessed 20% fusion-inducing ability and four p10 fusion-deficient mutants V15M, V19M, C21S and L32A reduced or lost their ability to activate RhoA and Rac1 signaling. We conclude that p10-mediated syncytium formation proceeds by utilizing RhoA and Rac1-dependent signaling.

Keywords

Acknowledgement

Supported by : National Science Council

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