Genome-wide RNAi screening for suppressors of a
vhp-1 deletion in C. elegansChun Li1, Naoki Hisamoto1, Tomoaki Mizuno1, Paola Nix2, Michael Bastiani2, Kunihiro Matsumoto11 Div.,of Biol. Sci., Grad. School of Sci., Nagoya Univ., Japan2 Div.,of Biol., Utah Univ., USAMitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and a wide variety of environmental stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun N-terminal kinase (JNK)-like mitogen-activated protein kinase (MAPK) signaling pathway, which consists of MIG-2 small G protein, MAX-2 MAPK kinase kinase kinase (MAP4K), SHC-1 adaptor protein, MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPK kinase (MAPKK), and KGB-1 JNK-like MAPK. It has been shown that the KGB-1 cascade is inactivated by VHP-1, a member of the MAPK phosphatase family, and that mutations defective in the components of the KGB-1 cascade strongly suppress the growth arrest caused by a
vhp-1 deletion. To identify additional components of KGB-1 cascade, we performed a genome-wide RNA interference (RNAi) screening for suppressors of the
vhp-1 deletion. As the result, genes encoding various factors, including protein kinases, transcription factors, mediator complexes, a receptor-like transmembrane protein and an RNA-binding protein were identified. Interestingly, genes required for neuroregeneration, such as DLK-1, PMK-3 and CEBP-1, were also identified as
vhp-1 suppressors. Here, we describe a novel finding that a receptor-like transmembrane protein identified by this screening is required for neuronal regeneration in C. elegans.