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Question

What is the main function of Rab GTPases in protein trafficking?

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Explanation

Rab family is largest branch of Ras superfamily, more than sixty members in mammals, each localized to specific organelle defining compartment identity and regulating sequential vesicle traffic steps. C-terminal cysteine geranylgeranylation anchors Rab to cytosolic face of membranes. In active GTP-bound conformation, Rab recruits diverse effectors: tethering complexes EEA1 for Rab5 early endosomes, GARP and golgins for retrograde traffic, exocyst for Rab11 recycling vesicles, and motor adaptors linking vesicles to kinesin for anterograde or dynein-dynactin for retrograde movement along microtubules. Guanine exchange factors like Rabex-5 activate Rabs on designated membranes, while RabGAPs containing TBC domain stimulate hydrolysis converting to GDP form releasing effectors and allowing extraction by GDI for recycling. This cycle ensures specificity so COPII vesicles from ER fuse only with cis-Golgi, not lysosomes, and provides timing for endosomal maturation Rab5 to Rab7 conversion. Unlike importin transporting through nuclear pores or kinases phosphorylating SNAREs to regulate fusion, Rab orchestrates upstream vesicle targeting, motility and tethering coordinated with SNARE-mediated final fusion ensuring fidelity of trafficking pathways and organelle biogenesis.