RabGTPaser

Rab GTPases, sometimes referred to as RabGTPases, are a large family of small GTP-binding proteins that regulate intracellular vesicle trafficking in eukaryotic cells. In humans, the Rab family comprises around 60 members. They act as molecular switches cycling between an active GTP-bound state and an inactive GDP-bound state, controlled by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The switch is tightly coordinated by GDP-dissociation inhibitors (GDI) that shuttle Rab proteins between membranes and the cytosol.

Rab proteins associate with specific membranes via post-translational lipid modification, typically geranylgeranylation at two C-terminal cysteines, installed by Rab geranylgeranyltransferase in a complex with Rab escort protein (REP). This membrane targeting underpins their role in distinct steps of vesicle trafficking: budding, movement along cytoskeletons, tethering, and fusion with target membranes. Each Rab recruits specific effector proteins that mediate docking, motor-driven movement, and SNARE complex assembly.

Examples of functionally well-characterized Rabs include Rab5 (early endosomes), Rab7 (late endosomes/lysosomes), Rab11 (recycling endosomes), and Rab27A (secretory granules).

Dysregulation or mutation of Rab GTPases is linked to human disease; notable examples include Rab27A in Griscelli syndrome type 2, Rab7 in certain forms of Charcot–Marie–Tooth disease, and Rab38 in Hermansky–Pudlak syndrome. Beyond rare diseases, Rab dysregulation is implicated in cancer and neurodegenerative conditions due to altered trafficking pathways.

Rab GTPases are frequently studied as markers of trafficking pathways and as potential targets to modulate vesicular transport in research and therapeutic contexts.