RGS proteins (regulators of G protein signaling) inhibit G protein signaling by binding directly to G protein alpha subunits and converting them from their active GTP-bound form to their inactive GDP-bound form. We have previously described the C. elegans RGS protein EGL-10 protein, which is expressed in most or all C. elegans neurons and inhibits signaling by the G protein GOA-1 to regulate several behaviors, including egg laying and locomotion. We found that both the mammalian and C. elegans genomes encode large families of proteins that share sequence similarity with EGL-10 in the ~120 amino acid "RGS domain", the part of these proteins that interacts with G protein alpha subunits. To help understand why there might be so many G protein regulators, we have analyzed the expression patterns and functions of all 11 RGS genes identified so far by the C. elegans genome sequencing project. We used GFP reporter transgenes to examine the expression patterns of the RGS genes. Our results suggest that about half of the RGS genes in C. elegans are expressed quite widely, and have expression patterns that overlap extensively. For example,
egl-10, C05B5.7, C41G11.3, and the RGS genes on cosmids C16C2 and F45B8 each appear to be expressed in most or all neurons, and B0336.4 appears to be expressed in the neurons as well as most other cells in the animal. Because these genes do not all have the same functions (for example,
egl-10 has a mutant phenotype, and thus is not completely redundant with the other RGS genes expressed in the same cells), we suggest that different RGS proteins may achieve specific functions by acting specifically on different G protein targets. Five RGS genes in C. elegans appear to be expressed in patterns that are highly spatially and/or temporally restricted. These RGS proteins may achieve specific functions in part by virtue of this fact. For example, GFP reporters for C29H12.3 are expressed only in seven amphid neurons and the two phasmid neurons. This suggests a specific role for this RGS gene in down-regulating or desensitizing responses to the chemosensory or mechanosensory stimuli detected by these cells through G protein signaling pathways. We have begun to examine the functions of the RGS genes by analyzing animals that overexpress them from multicopy transgenes. Overexpression of
egl-10 in this manner gives a phenotype similar to that obtained by deleting the gene for its known G protein target, GOA-1. We hope that overexpression of the other RGS genes will similarly result in gain-of-function phenotypes for these genes. As described in abstracts for this meeting by Meng-Qiu Dong and Georgia Patikoglou, two additional RGS genes besides
egl-10, when overexpressed, also stimulate egg laying, presumably by also inhibiting the G protein GOA-1. These RGS genes, C05B5.7 and F16H9.1, appear to be expressed in patterns that overlap the GOA-1 expression pattern in the nervous system, consistent with this idea. Another RGS gene, on cosmid C16C2, also appears to be widely expressed in the nervous system, but causes an opposite phenotype when overexpressed. This RGS gene could encode an inhibitor of EGL-30, a G protein that activates egg laying. We are further testing these ideas by examining loss-of-function mutations in the RGS genes.