Small GTPases

Abstract

Members of the protein superfamily of small guanosine triphosphatases, also known as small GTPases, small G-proteins, or the Ras superfamily, are involved in nearly every aspect of cell biology. Small GTPases are tightly regulated molecular switches that make binary on/off decisions through controlled loading of GTP (activation) and hydrolysis of GTP to GDP (inactivation). Small GTPases typically function as nodal points that integrate broad upstream regulatory inputs and disseminate broad effector outputs. The superfamily comprises five families that are conserved across eukaryotes: Ras, Rho, Rab, Arf, and Ran. Each family, besides Ran, has radiated functionally since our last common ancestor with fungi, and certain subfamilies persist throughout metazoa. The double genome duplication leading to vertebrates resulted in two to four genes for many subfamilies, plus some novel mammalian additions. Here we discuss general principles of small GTPase biology, survey the C. elegans complement of small GTPases and how they compare to their mammalian counterparts, and note atypical nematode members that do not fall into discrete subfamilies. We do not discuss the multitude of other proteins with catalytic guanosine triphosphatase domains that fall outside the small GTPase/Ras superfamily.