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Effect of HSV”. essential for transcytosis. In this study, carried AP1903 out with the human being oligodendrocytic cell collection HOG, we display that PLP colocalized with green fluorescent protein (GFP)-MAL2 after internalization from your plasma membrane. In addition, both immunoprecipitation and immunofluorescence assays, indicated the living of an connection between GFP-MAL2 and PLP. Finally, ultrastructural studies shown colocalization of GFP-MAL2 and PLP in vesicles and tubulovesicular constructions. Taken together, these results demonstrate for the first time the connection of PLP and MAL2 in oligodendrocytic cells, assisting the transcytotic model of PLP transport previously suggested. Intro The myelin sheath is an electrically insulating coating that surrounds axons in both the central and peripheral nervous systems. Oligodendrocytes (OLs) are the glial cells that produce myelin in the central nervous system (CNS) [1], [2]. The presence of myelin sheath and its discontinuities, the nodes of Ranvier, allows saltatory conduction of action potential. In the absence of myelin, the velocity of nerve impulse conduction would be pathologically sluggish. To form the myelin sheath, OLs wrap their processes -extensions of the plasma membrane- round the axons [3], providing rise to different membrane domains and subdomains [4]. The various subdomains of OLs plasma membrane are not separated, as it happens with Rabbit Polyclonal to DARPP-32 basolateral and apical domains of epithelial polarized cells. However, the myelin composition is definitely drastically different from that of the plasma membrane of the cell body since, similar to the apical membrane of epithelial cells, myelin sheath is definitely rich in glycosphingolipids (GSLs) and cholesterol [5]. Consequently, although myelinating OLs do not polarize segregating standard apical and basolateral surface subdomains, they can be considered as polarized cells [6]. The formation of the myelin sheath in the CNS is definitely a highly complex process which involves the synthesis, transport, and target of large amounts of membrane proteins and lipids by OLs [7]. During OLs differentiation, several proteins and lipids segregate to form the myelin sheath. In spite of myelin composition, standard of the apical plasma membrane of polarized cells, studies showed that myelin sheet biogenesis offers features of basolateral traffic. In this regard, vesicular stomatitis disease G protein (VSV-G), a basolateral marker, accumulated in the myelin sheet, whereas influenza disease hemagglutinin (HA), an apical marker, accumulated in the plasma membrane of the cell body, suggesting the myelin membrane is the target of a basolateral-type pathway [8], [9]. PLP, the major myelin protein, is an integral membrane protein with four transmembrane domains. PLP and DM20, a smaller isoform generated by alternate splicing, are the most abundant proteins in the CNS myelin, comprising the 50% of total myelin proteins [1]. PLP has been associated with the low-density CHAPS-insoluble membrane portion in cultured OLs [10], although integration of PLP into different membrane domains is definitely a dynamic process that depends on the trafficking stage. OLs lacking PLP are still capable of myelinating axons, although physical stability of myelin decreases, since PLP is responsible for the compaction of myelin sheaths [11]. Mutations of the PLP gene cause dysmyelinating diseases in man and animals, such as Pelizaeus-Merzbacher disease, an X-linked recessive leukodystrophy [12], [13]. Important points on PLP traffic possess still to be elucidated concerning its transport to the myelin sheath. After its synthesis in the endoplasmic reticulum, PLP is definitely transported AP1903 to the Golgi by vesicular traffic. It is yet, not entirely obvious how PLP reaches its final destination, the myelin sheath. However, several studies suggest that PLP could reach the myelin sheath indirectly via the plasma membrane of the cell body rather than directly from the Golgi. This transcytotic route is similar to that observed for many apical AP1903 proteins in hepatocytes, via the basolateral surface [6], [14]. If PLP travels by transcytosis, it is tempting to suggest a feasible association of this myelin protein with MAL2, a raft protein essential for transcytosis in.