Abstract
The velocity of the nerve impulse conduction of vertebrates relies on the myelin sheath, an electrically insulating layer that surrounds axons in both the central and peripheral nervous systems, enabling saltatory conduction of the action potential. Oligodendrocytes are the myelin-producing glial cells in the central nervous system. A deeper understanding of the molecular basis of myelination and, specifically, of the transport of myelin proteins, will contribute to the search of the aetiology of many dysmyelinating and demyelinating diseases, including multiple sclerosis. Recent investigations suggest that proteolipid protein (PLP), the major myelin protein, could reach myelin sheath by an indirect transport pathway, that is, a transcytotic route via the plasma membrane of the cell body. If PLP transport relies on a transcytotic process, it is reasonable to consider that this myelin protein could be associated with MAL2, a raft protein essential for transcytosis. In this study, carried out with the human oligodendrocytic cell line HOG, we show that PLP colocalized with green fluorescent protein (GFP)-MAL2 after internalization from the plasma membrane. In addition, both immunoprecipitation and immunofluorescence assays, indicated the existence of an interaction between GFP-MAL2 and PLP. Finally, ultrastructural studies demonstrated colocalization of GFP-MAL2 and PLP in vesicles and tubulovesicular structures. Taken together, these results prove for the first time the interaction of PLP and MAL2 in oligodendrocytic cells, supporting the transcytotic model of PLP transport previously suggested.
Highlights
The myelin sheath is an electrically insulating layer that surrounds axons in both the central and peripheral nervous systems
Endogenous and exogenous MAL2 were up-regulated when cultured in differentiation medium (DM) and culturing of both cell lines in differentiation conditions resulted in an increase of proteolipid protein (PLP) detection
In a previous work [26], we characterized a MAL2-positive compartment in the oligodendrocytic cell lines Oli-neu and HOG, showing that, after differentiation, these cells up-regulate the expression of MAL2, which is accumulated in an intracellular compartment exhibiting some of the main features of the apical recycling endosome (ARE)/ subapical compartment (SAC), such as colocalization with Rab11a and CD59, pericentrosomal location, tubulovesicular morphology, sensitivity to disruption of the microtubule cytoskeleton with nocodazole and lack of internalized transferrin
Summary
The myelin sheath is an electrically insulating layer 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]. To form the myelin sheath, OLs wrap their processes extensions of the plasma membrane- around the axons [3], giving rise to different membrane domains and subdomains [4]. The various subdomains of OLs plasma membrane are not separated, as it occurs with basolateral and apical domains of epithelial polarized cells. Myelinating OLs do not polarize segregating typical apical and basolateral surface subdomains, they can be considered as polarized cells [6]
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