Rab (G-protein)

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The Rab family of proteins is a member of the Ras superfamily of GTPases, or enzymes that can bind and hydrolysis hydrolyze Guanosine triphosphate. Approximately 70 types of Rabs have now been identified in humans. Some types of Rabs are involved in the release of neurotransmitters from synaptic vesicles.

Rab proteins are post translationally modified by the addition of (usually) two geranylgeranyl groups to two C-terminal cystines. Geranylgeranylation is carried out by Rab geranylgeranyl transferase (RabGGTase or GGTaseII). The Rab escort protein (REP) is required to bind the Rab and to present it to the RabGGTase. After prenylation, the Rab escort protein binds the hydrophobic, insoluble geranylgeranyl groups and delivers the prenylated Rab to the relevant cell membrane. The lipid prenyl groups can then insert into the membrane, anchoring the Rab at the membrane. Because Rab proteins are anchored to the membrane by end of a flexible C-terminal chain they can be thought of as a 'balloon on a string'.

Once Rab proteins are bound to a vesicle surface they can be activated by the replacement of guanosine diphosphate with GTP (catalysed by Guanine nucleotide exchange factors, or GEFS). Rabs bound to GTP are in the active conformation and can now interact with or recruit Rab effectors on target membranes within the cell. Binding of Rab to a Rab effector tethers the vesicle to its appropriate target membrane and allows other membrane surface proteins (SNAREs) to interact, resulting in the docking of the vesicle to the target membrane. Now the Rab has fulfilled its function and the GTP is degraded to GDP (catalysed by Guaninuclease activating factors, or GAPs). The Rabs can then be recycled back to their membrane of origin. The GDP dissociation inhbitor (GDI) is necessary for the recycling pathway. This enzyme binds the prenylated Rab, inhibits the exchange of GDP for GTP (which would reactivate the Rab), solubilizes the prenyl groups, and delivers the Rab to its original membrane. GDI and REP proteins have related functions and are related enzymes.

Defects in prenylation can cause pathologies such as choroideremia.

[edit] Types

The approximately 70 different Rabs can be thought of as address labels for vesicle trafficking, defining the identity and routing of vesicles.

[edit] References

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