Rab GTPase Function in Endosome and Lysosome Biogenesis

Eukaryotic cells maintain a highly organized endolysosomal system. This system regulates the protein and lipid content of the plasma membrane, it participates in the intracellular quality control machinery and is needed for the efficient removal of damaged organelles. This complex network comprises an endosomal membrane system that feeds into the lysosomes, yet also allows recycling of membrane proteins, and probably lipids. Moreover, lysosomal degradation provides the cell with macromolecules for further growth. In this review, we focus primarily on the role of the small Rab GTPases Rab5 and Rab7 as organelle markers and interactors of multiple effectors on endosomes and lysosomes and highlight their role in membrane dynamics, particularly fusion along the endolysosomal pathway. Rab GTPases are key factors that determine organelle identity throughout the endomembrane system. Endosomes change identity by replacing Rab5 with Rab7, which requires the specific and tightly regulated recruitment of the Rab7 guanine nucleotide exchange factor (GEF) to the endosome membrane. Recent work on tethering proteins, including the lysosomal HOPS complex and the coiled-coil protein early endosome antigen 1 (EEA1), implies novel and conserved mechanisms of vesicle tethering and membrane fusion at organelles.