Insights into RGS protein function from studies in Caenorhabditis elegans

The nematode worm, Caenorhabditis elegans, contains orthologs of most regulator of G protein signaling (RGS) protein subfamilies and all four G protein α-subunit subfamilies found in mammals. Every C. elegans RGS and Gα gene has been knocked out, and the in vivo functions and Gα targets of a number of RGS proteins have been characterized in detail. This has revealed a complex relationship between the RGS and Gα proteins, in which multiple RGS proteins can regulate the same Gα protein, either by acting redundantly or by exerting control over signaling under different circumstances or in different cells. RGS proteins that are coexpressed can also show specificity for distinct Gα targets in vivo, and the determinants of such specificity can reside outside of the RGS domain. This review will discuss how analysis in C. elegans may aid us in achieving a full understanding of the physiological functions of RGS proteins.