Rab Family

Rab proteins are monomeric small guanine triphosphatases (GTPases) that function as key regulators of eukaryotic membrane trafficking. Specifically, they have been implicated in the budding, transport, docking, and fusion of lipid bilayer vesicles. The Rabs form the largest and most diverse branch of the Ras protein superfamily. They are evolutionarily conserved and are present in all eukaryotes investigated, localizing to specific organelles of the secretory and endocytic pathway. The human genome project has demonstrated the existence of approximately 70 members in the human Rab family, which can be divided into 10 subfamilies. Members of each subfamily have similar subcellular localization and some functional overlap. Most Rab proteins are ubiquitously expressed; however, a number such as Rab3A, which is expressed neurons, and Rab27, expressed in melanocytes and platelets, are cell-type specific. Rab proteins are characterized by their functional cycle. As their name suggests they bind guanine triphosphate (GTP), which results in their activation. The GTP can then be hydrolyzed to guanine diphosphate (GDP) resulting in the Rab adopting an inactive (GDP-bound) conformation and leading to its subsequent membrane dissociation. Several Rab-interacting proteins have been identified, which either regulate the Rab nucleotide-bound state, its localization, or act as effectors of Rab function.