CHM

Rab escort proteins (REPs) and Rab GDP-dissociation inhibitor (GDIs) mediate membrane association of Rab proteins.

CHM cycle

 Rab proteins are intrinsically soluble and require the post-translational covalent attachment of isoprenoid moieties to their C-termini for membrane association. Newly synthesized Rabs associate with REP and form a stable complex.

 The complex is a substrate for the heterodimeric Rab geranylgeranyl transferase (RabGGT), which attaches geranylgeranyl groups to C-terminal cysteines in Rabs.

 After lipid transfer, it is thought that REP delivers the prenylated Rab to the donor membrane and then recycles to bind other nascent Rab proteins. In the absence of REP or RabGGT, Rabs remain cytosolic and inactive.

 Rab GDP-dissociation inhibitor (GDI) is thought to retrieve Rab proteins from target membranes and maintain them in the GDP-bound (inactive) state in the cytosol in a stable complex.

 RabGDI eventually delivers Rabs back to the donor membrane and then recycles back to the cytosol so the cycle can restart.

 Both REP and GDI specifically bind the GDP-bound form of Rab.

 After GDI or REP dissociation from Rabs at the donor membrane, specific Rab guanine nucleotide exchange factors (GEF) replace GDP with GTP, thus activating Rabs to recruit effectors and preventing their membrane retrieval.

 Multiple isoforms of REP (REP-1, -2) and GDI (GDI α, β, γ) exist in mammalian cells and have been shown to be redundant in some, but not all situations.

See also

 REPs
 GDIs