Rab proteins and the compartmentalization of the endosomal system

Abstract

Of the approximately 70 human Rab GTPases, nearly three-quarters are involved in endocytic trafficking. Significant plasticity in endosomal membrane transport pathways is closely coupled to receptor signaling and Rab GTPase-regulated scaffolds. Here we review current literature pertaining to endocytic Rab GTPase localizations, functions, and coordination with regulatory proteins and effectors. The roles of Rab GTPases in (1) compartmentalization of the endocytic pathway into early, recycling, late, and lysosomal routes; (2) coordination of individual transport steps from vesicle budding to fusion; (3) effector interactomes; and (4) integration of GTPase and signaling cascades are discussed.

Figure 1.

Overview of Rab GTPases on the endocytic pathway. Rab GTPases function in internalization and transport to degradation, as well as recycling to the plasma membrane and the Golgi. For details regarding individual Rab GTPase function, refer to the text and Table 1.

Figure 2.

Rab GTPases integrate membrane trafficking events and signaling. Rab GTPases regulate cargo sorting, vesicle budding, membrane tabulation, cytoskeletal translocation, vesicle docking, and fusion. Rab GTPases decode extracellular signals to provide a coordinated response to physiological and metabolic demands. Select pathways are shown; not depicted are Rab-mediated interactions with the endoplasmic reticulum (ER) and other organelles for lipid exchange or interactions with the actin cytoskeleton.