The intestine plays an essential role in organism-wide regulatory networks in both vertebrates and invertebrates. In Caenorhabditis elegans, class 1 flr genes (
flr-1,
flr-3 and
flr-4) act in the intestine and control growth rates and defecation cycle periods, while class 2 flr genes (
flr-2,
flr-5,
flr-6 and
flr-7) are characterized by mutations that suppress the slow growth of class 1 flr mutants. This study revealed that
flr-2 gene controls antibacterial defense and intestinal color, confirming that
flr-2 regulates intestinal functions.
flr-2 encoded the only glycoprotein hormone alpha subunit in C. elegans and was expressed in certain neurons. Furthermore, FLR-2 bound to another secretory protein GHI-1, which belongs to a family of lipid- and lipopolysaccharide-binding proteins. A
ghi-1 deletion mutation partially suppressed the short defecation cycle periods of class 1 flr mutants, and this effect was enhanced by
flr-2 mutations. Thus, FLR-2 acts as a signaling molecule for the neural control of intestinal functions, which is achieved in a functional network involving class 1 and class 2 flr genes as well as
ghi-1. These results are informative to studies of glycoprotein hormone signaling in higher animals.