Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid/Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid, Spain.
PLoS One. 2011 May 9;6(5):e19388. doi: 10.1371/journal.pone.0019388.
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.
脊椎动物的神经冲动传导速度依赖于髓鞘,这是一种围绕中枢和周围神经系统轴突的电绝缘层,使动作电位跳跃式传导。少突胶质细胞是中枢神经系统中产生髓鞘的神经胶质细胞。更深入地了解髓鞘形成的分子基础,特别是髓鞘蛋白的运输,将有助于寻找许多脱髓鞘和脱髓鞘疾病(包括多发性硬化症)的病因。最近的研究表明,髓鞘蛋白中的主要蛋白 PLP 可能通过间接转运途径(即通过细胞体的质膜的胞吞作用途径)到达髓鞘鞘。如果 PLP 运输依赖于胞吞作用过程,那么可以合理地认为这种髓鞘蛋白可能与 MAL2 相关,MAL2 是胞吞作用所必需的筏蛋白。在这项使用人少突胶质细胞系 HOG 进行的研究中,我们表明 PLP 在从质膜内化后与绿色荧光蛋白(GFP)-MAL2 共定位。此外,免疫沉淀和免疫荧光测定均表明 GFP-MAL2 和 PLP 之间存在相互作用。最后,超微结构研究表明 GFP-MAL2 和 PLP 在小泡和管状小泡结构中共定位。总之,这些结果首次证明了 PLP 和 MAL2 在少突胶质细胞中的相互作用,支持了先前提出的 PLP 转运的胞吞作用模型。