The Tumor Necrosis Factor (TNF) receptor-associated factors (TRAFs) are adaptor/scaffold molecules that interact with members of the interleukin-receptor (ILRs) or TNFR families and function mainly in the immune system. TNF-alpha signaling promotes autosomal dominant polycystic kidney disease (ADPKD). In mammals, there are six TRAFs (1-6) that share a conserved C-terminal TRAF domain. The C. elegans genome does not encode a TNF Receptor but does encode a sole TRAF gene,
trf-1. In humans, mutations in the polycystin-1 (PC-1) or polycystin-2 (PC-2) ciliary mechanosensory complex cause ADPKD. In C. elegans, the polycystins LOV-1 and PKD-2 localize on the ciliary membrane and are required for male sensory behaviors. Hence, the connection between the polycystins and cilia seems to be an ancient one. We find that
trf-1 is co-expressed with
pkd-2 in the male specific CEM, RnB, and HOB neurons and is required for male mating behaviors. We are interested in exploring a potential connection between immune recognition and mate recognition. To this end, we examined the mating behavior and mating efficiency of mutant males defective in the Toll pathway including
tol-1 and
ikb-1 (I kappa beta homolog). We performed four mating behavioral (leaving, retention, response, and vulva location) and mating efficiency assays. Like
pkd-2 mutants,
trf-1(
nr2014) mutant males have response and Lov defects. In contrast,
tol-1;
him-5 and
ikb-1;
him-5 are not statistically different from the wild-type
him-5. In the mating efficiency assay,
trf-1;
him-5 and
pkd-2;
him-5 scored low and are not statistically different, whereas
tol-1 and
ikb-1 appear wild type.
trf-1;
him-5 and
pkd-2;
him-5 males are leaving assay (Las) defective, whereas
tol-1 and
ikb-1 are not Las. All mutant strains seem to be normal for the retention assay, indicating that these males can sense the presence of a mate. We conclude that
trf-1 acts like
pkd-2, suggesting the two function in a similar pathway. Genetic interactions between
trf-1 and components of the C. elegans PKD pathway (
lov-1,
pkd-2,
klp-6, and the cwp genes) are being examined. To ascertain the site of TRF-1 action, we are generating transgenic animals expressing a functional TRF-1::GFP. We will determine whether TRF-1 is required for the localization, stability, or signaling properties of or physically associates with polycystin pathway components.