Oligodendrocyte vesicle transport: role of Rab40c

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.