flr (fluoride resistant) mutations are classfied into two categories, class 1 and class 2. Class 1 mutations(
flr-1,
flr-3 and
flr-4) show many phenotypes, such as strong resistance to fluoride ion, slow growth, short defecation cycle periods, defects in the defecation expulsion step, synthetic abnormality in dauer formation,etc. These genes encode an ion channel of the DEG/ENaC superfamily, a kinase-like molecule, and a novel Ser/Thr protein kinase, respectively, which seem to constitute a regulatatory system in the intestine. Class 2 mutations(
flr-2 and
flr-5) confer weak resistance to fluoride ion and suppress the slow-growing phenotype and synthetic dauer abnormality (but not the defecation abnormality) of class 1 mutations. To elucidate how the class 1 flr regulatory system controls diverse functions, we cloned one of the class 2 flr genes, which probably act downstream of class 1 genes in the regulately cascade. FLR-2 is a secretory protein belonging to the DAN/Gremlin/ Cerberus family (TGF- antagonists). However, it remains to be studied whether FLR-2 antagonizes a soluble signaling molecule like TGF- or it acts, for instance, by binding to a membrane-bound receptor. Recently, we found that class 2 mutants show weak response to benzaldehyde, and that
flr-2 is expressed in a few sensory neurons. We plan to continue the analysis of the class 2 genes to elucidate the molecular mechanisms of growth-rate regulation and neural functions.