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¹ Structural Biology Center, National Institute of Genetics, Mishima 411-8540, Japan
² Technical Section, National Institute of Genetics, Mishima 411-8540, Japan
³ Department of Physiology, Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
⁴ Core Research of Evolutional Science & Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan
⁵ Department of Genetics, The Graduate University for Advanced Studies (Sokendai), Mishima 411-8540, Japan

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.

^aPresent address: Division of Brain Function, National Institute of Genetics, Mishima 411-8540, Japan.

^bPresent address: Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.

^cPresent address: Department of Biology, Graduate School of Science, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.

^* Correspondence: ikatsura{at}lab.nig.ac.jp