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KMID : 0578320080260040396
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Molecules and Cells
2008 Volume.26 No. 4 p.396 ~ p.403
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Activation of Small GTPases RhoA and Rac1 Is Required for Avian Reovirus p10-induced Syncytium Formation
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Liu Hung-Jen
Lin Ping-Yuan Tzu
Wang Ling-Rung
Hsu Hsue-Yin
Liao Ming-Huei
Shih Wen-Ling
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Abstract
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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-kappaB 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.
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KEYWORD
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avian reovirus, p10, syncytium, RhoA, Rac1
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