Intracellular Trafficking and Signaling: The Role of Endocytic Rab GTPase
M. Alejandro Barbieri, Marisa J. Wainszelbaum and Philip D. Stahl
Binding of growth factors and other cell-activating agents to cell surface receptors is known to trigger a complex series of events that initiate signal transduction. Ligand activation of many signal-transducing receptors accelerates receptor endocytosis. The classical view is that receptor internalization is primarily a mechanism of signal attenuation and receptor degradation, but more recent evidence suggests that internalization may mediate the formation of specialized signaling complexes on intracellular vesicles. The small Rab GTPases, master regulators of vesicle transport, can influence both receptor trafficking and receptor signaling pathways. They are localized to specific organelles and domains where they not only mediate vesicle docking and fusion but also influence the recruitment of effector proteins that mediate signal transduction and vesicle motility. It is interesting to speculate that extracellular stimuli contribute to the endocytosis of cell surface components for survival, defense, repair, storage and degradation. In addition, traffic regulation by external stimuli emphasizes the possible role in infection, aging, cancer and several degenerative diseases. Thus, receptor-mediated endocytosis regulation by small Rab GTPases not only provides a mechanism for attenuation of signaling but may also determine the quality of signal output by providing different combinations of downstream effectors at various endocytic compartments.