title: C. elegans Rassf homolog, rasf-1, is functionally associated with rab-39 Rab GTPase in oxidative stress response.
abstract: The Ras association domain family (Rassf) is one of the Ras effectors, which can bind to several GTP-charged Ras-like GTPases. The Rassf proteins are widely conserved beyond species from nematode to human. To explore the novel functions of Rassf proteins, we took advantage of nematode C. elegans as a model animal with only one Rassf homolog, T24F1.3 (rasf-1). The rasf-1-mutant as well as rasf-1-knockdown animals were found to be more sensitive to oxidative stress of arsenite than in wild type, indicating that rasf-1 is involved in oxidative stress response. We next screened for proteins that interact with RASF-1 by the yeast two-hybrid system and identified RAB-39 Rab GTPase as an interacting partner of RASF-1. We not only confirmed specific binding between these molecules but also demonstrated that RASF-1 binds to GTP-bound form but not GDP-bound form of RAB-39. Importantly, rab-39 mutant animals were also sensitive to oxidative stress, which was dependent on rasf-1 according to the epistasis analysis. Moreover, Rassf1 and Rab39, mammalian homologs of rasf-1 and rab-39, respectively, were shown to interact with each other in vitro. These results indicate that the RASF-1 functionally interacts with RAB-39 and that the interaction between their homologs is conserved in mammals.
authors.affiliation: Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Nojihigashi, Kusatsu, Shiga, 525-8577, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Takenaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Inoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeshima
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kakura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hori
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011485:Protein Binding; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018053:Arsenites; D029742:Caenorhabditis elegans Proteins; C578982:RSF-1 protein, C elegans; C582658:Rab-39 protein, C elegans; D020691:rab GTP-Binding Proteins; C015001:arsenite