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Rab8

Rab8 (Ras-related proteins in brain 8) is a 24 kDa protein that belongs to the Rab GTPase family (7). Rab proteins are known for their participation in and regulation of intracellular membrane trafficking pathways (17, 45, 47). In their active GTP-bound state different Rab proteins bind to different membrane compartments and recruit specific effector proteins, which are not only involved in docking and fusion with the target membrane but also in the formation of transport vesicles and in binding motor proteins for vesicle transport (17, 18, 27, 44, 47).

Rab8 displays high homology with the yeast S. cerevesiae protein SEC4 involved in post-Golgi traffic (16, 24) and with the S. pombe protein Ypt2p that acts as well in the last stage of the secretory pathway (4). In humans there are two isoforms with 80% homology, Rab8a and Rab8b, which have a differential expression pattern (Figure 1). Rab8b is expressed in spleen, testis and brain (2, 8) while Rab8a is more ubiquitous expressed but shows low expression levels in the three organs (8). Nevertheless, Rab8a and Rab8b have been shown to play a similar role in vesicular traffic from the Golgi complex to the plasma membrane in regulated secretion in ATt20 cells (8). The Rab8 lipid motif differs from other Rabs resulting in only one geranylgeranylation (3, 26). A preliminary X-ray crystallographic analysis of mammalian Rab8 in complex with the nucleotide exchange factor MSS4 has been published (25).