Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes.
Rab proteins comprise a family of small GTPases that serve a regulatory role in vesicular membrane traffic. Geranylgeranylation of these proteins on C-terminal cysteine motifs is crucial for their membrane association and function. This post-translational modification is catalysed by rab geranylgeranyl transferase (Rab-GGTase), a multisubunit enzyme consisting of a catalytic heterodimer and an accessory component, named rab escort protein (REP)-1. Previous in vitro studies have suggested that REP-1 presents newly synthesized rab proteins to the catalytic component of the enzyme, and forms a stable complex with the prenylated proteins following the transfer reaction. According to this model, a cellular factor would be required to dissociate the rab protein from REP-1 and to allow it to recycle in the prenylation reaction. RabGDP dissociation inhibitor (RabGDI) was considered an ideal candidate for this role, given its established function in mediating membrane association of prenylated rab proteins. Here we demonstrate that dissociation from REP-1 and binding of rab proteins to the membrane do not require RabGDI or other cytosolic factors. The mechanism of REP-1-mediated membrane association of rab5 appears to be very similar to that mediated by RabGDI. Furthermore, REP-1 and RabGDI share several other functional properties, the ability to inhibit the release of GDP and to remove rab proteins from membranes; however, RabGDI cannot assist in the prenylation reaction. These data suggest that REP-1 is per se sufficient to chaperone newly prenylated rab proteins to their target membranes.
Alexandrov
K
K
European Molecular Biology Laboratory, Heidelberg, Germany.
Horiuchi
H
H
Steele-Mortimer
O
O
Seabra
M C
MC
Zerial
M
M
D019883:Alkyl and Aryl Transferases; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D020730:Guanine Nucleotide Dissociation Inhibitors; D007668:Kidney; D008565:Membrane Proteins / Q000378:metabolism*; D017368:Protein Prenylation; D014166:Transferases / Q000378:metabolism*; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins
D002352:Carrier Proteins; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D008565:Membrane Proteins; D000090802:rab7 GTP-Binding Proteins; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase; D019204:GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins