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Intracellular membrane trafficking plays an essential role in the biogenesis and maintenance of myelin. Members of the Rab protein family are important components of the systems that regulate intracellular vesicle transport. We examine the function of rRab22b, a novel rat Rab protein cloned from an oligodendrocyte cDNA library, by visualizing and identifying in living Hela cells the organelles that contain rRab22b. Our results show that rRab22b is present in the trans Golgi/TGN and endocytic compartments. Trafficking of membranes from trans Golgi to endocytic compartments takes place via small tubulo vesicular organelles containing rRab22b. The formation of vesicles in the trans Golgi also appears to be regulated by rRab22b. Additionally, our results suggest that rRab22b controls the transport of vesicles from the trans Golgi to endocytic compartments that localize in oligodendrocyte processes. That rRab22b is involved in the transport of certain proteins from trans Golgi to myelin is suggested by the evidence that certain proteins being targeted to the plasma membrane are first transported from trans Golgi to endocytic compartments. J. Neurosci. Res. 66:1149‐1160, 2001. © 2001 Wiley-Liss, Inc.

Intracellular membrane trafficking plays an essential role in the biogenesis and maintenance of myelin and regulation is necessary to maintain the structural and functional organization of the oligodendrocytes. Exocytic events are involved in the targeting of proteins synthesized in the endoplasmic reticulum such as proteolipid protein, DM20 and MAGs. Endocytic events also play an important part in the formation and maintenance of myelin as indicated by endocytosis in oligodendrocyte processes and myelin domains. Rab proteins are key components in mechanisms that regulate intracellular membrane trafficking. We cloned a novel oligodendrocyte Rab protein, designated Rab40c from its homology with Rab40. The cDNA sequence of Rab40c and the deduced amino acid sequence show an 843 base open reading frame indicating a protein with 281 amino acids. This protein has a deduced molecular of weight 31 466 Da and an isoelectric point of 9.83. Rab40c presents a number of distinct structural features including a carboxyl terminal extension and the occurrence of amino acid substitutions in the consensus sequence of the GTP-binding motifs. The carboxyl terminal region contains motifs that indicated possible isoprenylation and palmitoylation. Rab40c is localized in the perinuclear endocytic recycling compartment suggesting that it is involved in the regulation of endocytic events such as the recycling of receptors. The importance of this recycling in myelin formation is indicated by the increase in Rab40c mRNA with differentiation of oligodendrocytes.