PTR-15 is one of 24 C. elegans proteins sharing homology to the Hedgehog receptor Patched. PTC and PTR proteins carry both sterol-sensing and RND domains as well as 12 predicted transmembrane domains. Earlier work revealed that several of the PTR proteins are involved in molting (Zugasti et al. 2005). Other work showed that
bus-13, which exhibits surface abnormalities and sensitivity to some bacterial pathogens (Gravato-Nobre et al. 2005, Hodgkin et al. 2013), carries a missense mutation in
ptr-15. Fluorescent transgenic reporters further showed that
ptr-15 is expressed strongly in pharynx and intestinal cells and weakly in the epidermis. Recently, CRISPR/Cas9 was used to generate a
ptr-15 deletion allele, which exhibits a larval lethal arrest phenotype. This lethality, as well as pathogen sensitivity, is fully rescued by wildtype
ptr-15::mRFP transgenes. The larval lethality is also rescued by intestinal
ptr-15 expression driven from the
mtl-2 promoter, which surprisingly does not rescue the pathogen sensitivity, suggesting that normal pathogen resistance requires epidermal expression. Further characterization of the
ptr-15(null) phenotype is in progress. The missense mutant (pka
bus-13) grows normally on E. coli, but unlike wildtype,
bus-13 mutants are completely inviable in the presence of the bacterial pathogen Leucobacter Verde1, owing to lethal surface infection. Large scale selections for suppressor mutations allowing viability of this mutant on Verde1 have yielded two intragenic partial revertants, which have implications for PTR-15 structure and function. Surprisingly, none of the known and expected Verde1-resistance mutants were recovered in these selections, suggesting that the role of
ptr-15 in generating surface coat is distinct from that of other bus and srf genes. We are investigating the possibility that both intestinal and epidermal functions of PTR-15 are involved in transport of lipids or other small molecules.