In addition to TGF-beta like pathway, insulin/insulin-like growth factor-I signaling (IIS) pathway regulates larval diapause in the nematode Caenorhabditis elegans. To date, many of 40 genes encoding a putative insulin-like peptide have been identified. As for their receptor molecule, however, only DAF-2 protein has been identified as a sole insulin receptor homolog in the organism. It seems intriguing that forty kinds of ligands are bound to only one common receptor. On the other hand, in mammals, insulin-family peptides consisting of insulin, insulin-like growth factors (IGFs), and relaxins are bound to their own distinct receptor. Furthermore, as for IGF-II and relaxins, their receptors are a G protein-coupled receptor (GPCR) type and structurally different from those of insulin and IGF-I. Therefore, there is a possibility that distinct types of receptors for insulin-like molecules exist in C. elegans. A search on the WormBase for IGF-II and relaxin receptors revealed two GPCR genes,
fshr-1 and K03A1.2. Using gene-disrupted animals in addition to RNAi, we proved that these genes are related to larval diapause. Next, we elucidated crosstalk of these genes with IIS, TGF-beta like, and steroid pathways that are known to regulate larval diapause. As a result, regulation of larval diapause by these genes does not depend on IIS and TGF-beta like pathways. However, the regulation is fully dependent on the steroid pathway. Therefore, we here propose that
fshr-1 and K03A1.2. provide a new pathway regulating larval diapause and their pathways are integrated in the steroid pathway, as well as IIS and TGF-beta like pathways. We are going to identify Galpha subunits that are coupled with products of
fshr-1 and K03A1.2.