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Loss of a receptor-type guanylyl cyclase GCY-22 suppresses the chemotaxis defect of daf-18 mutants. (A) pe902, pe905, pe917, and pe922 were obtained in a suppressor screen for mutations that rescue the chemotaxis defect of daf-18(e1375) mutants. Naive animals were tested for NaCl chemotaxis. A deletion mutation gcy-22(tm2364) also suppresses the chemotaxis defect of the daf-18 mutants. (B) pe902, pe905, pe917, pe922, and tm2364 cause defects in attraction behavior to the ASER-sensed chemical ammonium chloride. (C) Genomic structure of gcy-22 receptor-type guanylyl cyclase. Solid boxes indicate predicted protein domains. Locations of the four suppressor mutations in the gcy-22 gene are depicted. Error bars represent standard error of the mean (SEM). (***) P




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To further investigate how the insulin/PI 3-kinase signaling modulates ASER function to regulate salt chemotaxis, we screened for suppressors of the chemotaxis defect in daf-18 mutants. Suppressor mutants were expected to show salt attraction similar to wild-type animals in the daf-18 genetic background. About 30,000 EMS-mutagenized haploid genomes were screened in the daf-18(e1375) genetic background by salt chemotaxis assay (see materials and methods). Through the screening, we obtained 23 suppressor mutants (data not shown). Of these, four suppressor mutations, pe902, pe905, pe917, and pe922, which clearly suppressed the chemotaxis defect of the daf-18 mutant, were picked up for further analysis (Figure 1A).


The suppressor mutations pe902, pe905, pe917, and pe922, were mapped by using the SNPs between the N2 strain and the CB4856 strain (Wicks et al. 2001). All of these suppressor mutations were mapped to the left arm of chromosome V and resided between two SNPs, pkP5135 and cE5-269. This region contains the gcy-22 gene, which is required for attraction to ASER-sensed ions including chloride ion (Ortiz et al. 2009). The four alleles caused reduced attraction to ammonium chloride in the wild-type background, similar to the deletion mutant, gcy-22(tm2364) (Figure 1B). The tm2364 mutation suppressed chemotaxis defect of the daf-18(e1375) mutant (Figure 1A), indicating that loss of gcy-22 improves chemotaxis of daf-18 mutants. By sequencing the gcy-22 genomic region of each suppressor mutant, nonsense and missense mutations were identified (Figure 1C; Figure S2; materials and methods). 041b061a72


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