Each Rab specifically targets to a membrane compartment and controls several factors, such as protein and lipid composition of the membrane, fusion between distinct compartments, vesicle motility along microtubules, and interaction with the cytoskeleton. The membrane targeting process, as well as specific binding to GDI, requires post-translational isoprenylation (geranylgeranyl moieties) of the two Cys residues at or near the C-terminus of Rab (Chavrier et al., 1991; Ullrich et al., 1993). √
Rab proteins, as all GTPases, alternate between an active state (GTP-bound) and an inactive state (GDP-bound). The mechanism for activation is common for all GTPase proteins and it is tightly regulated. At the beginning, the Rab protein is in the cytoplasmic pool in its inactive form, bound to GDP. In the GDP-bound form, they associate with a guanine dissociation inhibitor (GDI), which stabilizes the inactive Rab in the cytosol. In order to be activated, GDP has to be a changed to GTP. This reaction is facilitated by one or more guanine nucleotide exchange factors (GEFs). Due to the high cytosolic concentration of GTP (~1mM), it is ensured that GTP binds to Rab as soon as GDP has been released. …show more content…
To terminate their activity, there has to be a conversion from the GTP- to the GDP-bound form through GTP hydrolysis. The hydrolysis of GTP to GDP is not only driven by the GTPase activity of the protein itself. GTPase-activating proteins (GAPs) have an important role terminating the activity of the Rab protein. Once in the GDP-bound form, the Rab protein is ready to start a new cycle (Figure X: Rab
Rab proteins, as all GTPases, alternate between an active state (GTP-bound) and an inactive state (GDP-bound). The mechanism for activation is common for all GTPase proteins and it is tightly regulated. At the beginning, the Rab protein is in the cytoplasmic pool in its inactive form, bound to GDP. In the GDP-bound form, they associate with a guanine dissociation inhibitor (GDI), which stabilizes the inactive Rab in the cytosol. In order to be activated, GDP has to be a changed to GTP. This reaction is facilitated by one or more guanine nucleotide exchange factors (GEFs). Due to the high cytosolic concentration of GTP (~1mM), it is ensured that GTP binds to Rab as soon as GDP has been released. …show more content…
To terminate their activity, there has to be a conversion from the GTP- to the GDP-bound form through GTP hydrolysis. The hydrolysis of GTP to GDP is not only driven by the GTPase activity of the protein itself. GTPase-activating proteins (GAPs) have an important role terminating the activity of the Rab protein. Once in the GDP-bound form, the Rab protein is ready to start a new cycle (Figure X: Rab