FLR‐2, the glycoprotein hormone alpha subunit, is involved in the neural control of intestinal functions in Caenorhabditis elegans

Abstract

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.

Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans

“…The ortholog FSHR-1 is involved in innate immunity, stress responses, and germline fertility (69)(70)(71). The C. elegans genome also encodes two genes, flr-2 and T23B12.8, for α and β glycoprotein subunits (72,73). It will be interesting to see whether TRH-like signaling regulates the release of invertebrate glycoproteins, similar to its function in vertebrates, or whether its role in these species points to a different ancestral function.…”

Structure–Function Relationships of Glycoprotein Hormones and Their Subunits’ Ancestors

“…Nevertheless, it was not clear from these papers whether GPA2 and GPB5 were chemically cross-linked in GPA2/GPB5 heterodimers used in the bioactivity studies. Thus, it cannot be ruled out that GPA2 and/or GPB5 exert biological functions of their own (48, 49). …”

“…In Caenorhabditis elegans , only one GPCR gene with LRRD has been identified ( fsh-r1 ) that exhibits the highest similarity with FSHR among mammalian GPHR and plays a role in innate immune response (110). In this species, genes apparented to GPA2 ( flr-2 ) and GPB5 ( flr-5 ) were identified and might regulate FSH-R1 in the neural control of intestinal functions (49), maybe including intestinal ion-transport and/or intestinal immune defense.…”

Developmental tracing of luteinizing hormone β‐subunit gene expression using green fluorescent protein transgenic medaka (Oryzias latipes) reveals a putative novel developmental function

“…Their endogenous physiological function, however, remains to be elucidated. These hormones are attributed various functions in the gut in D. melanogaster (Sellami et al, 2011) and C. elegans (Oishi et al, 2009), including antibacterial defense, intestinal color change, defecation cycling, and possible water reabsorption. A putative function for LH in the gut during development could thus represent an evolutionarily redundant glycoprotein function, whereas in higher vertebrates Gpa2 and Gpb5 could possibly have assumed a thyrotropic function.…”

“…As these proteins are found in invertebrates, it has been suggested that they represent an ancestral glycoprotein (Roch et al, 2011). In addition to a putative thyrotropic effect in mammals, GPB5 and GPA2 have been suggested to function as an insect anti-diuretic hormone (Sellami et al, 2011) and to act as a neural signaling molecule controlling intestinal function in nematodes (Oishi et al, 2009). …”