Rab escort proteins

Disorder characterized by atrophy ofthe choroid (the thin membrane covering most of the posterior of the eye between the retina and sclera) and degeneration of the retinal pigment epithelium resulting in night blindness. The disease is caused by mutations in Rab escort protein Repl (component A of Rab geranylgeranyl transferase). 

Disorders caused by the impairment of the Golgi apparatus and further vesicular trafficking (e.g., mutations in the Rab escort protein Repl leading to choroideremia). 

Scheme 2 Intracellular processing of Rab proteins. Rab proteins form a complex with REP (Rab escort protein) that Is subsequently recognized by Rab GGTase-II and leads to geranylgeranylation of Rab.

S, Q, A, or C, whereas GGTase-I recognizes CaaX boxes with X = L or F. Other prenylated proteins, such as the Rab proteins involved in vesicular transport, terminate in a CC, CXC, or CC(X) , 3 motif these proteins are substrates for protein geranylgeranyltransferase type II (GGTase-II) [3]. In order to be prenylated, Rab proteins must associate with Rab escort protein after geranylgeranylation, Rab escort protein delivers the prenylated Rab to membranes. 

Prenylated small GTPases represent major hubs in most membrane-connected signaling networks. Rab prenylation is mediated by Rab geranylgeranyl transferase (RabGGTase), which works together with an adaptor protein, Rab escort protein (REP). Rab cycling between membranes and the cytosol is made possible by interaction with the GDP dissociation inhibitor (GDI). Both GDI and REP function as molecular chaperones, which can solubilize the prenylated Rab proteins in the cytosol. 

Wu, Y.W., Tan, K.T., Waldmann, H., Goody, R5, and Alexandrov, K. (2007) Interaction analysis of prenylated Rab GTPase with Rab escort protein and GDP dissociation inhibitor explains the need for both regulators. Proc. Natl. Acad. Scl U.S.A., 104, 12294-12299. 

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