Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes.

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2021-01-01 DOI:10.1177/17590914211009851
Robert P Skoff, Denise Bessert, Shreya Banerjee, Xixia Luo, Ryan Thummel
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引用次数: 1

Abstract

A founder mutation in human VPS11 (Vacuolar Protein Sorting 11) was recently linked to a genetic leukoencephalopathy in Ashkenazi Jews that presents with the classical features of white matter disorders of the central nervous system (CNS). The neurological deficits include hypomyelination, hypotonia, gradual loss of vision, and seizures. However, the cells expressing the mutation were not identified. Here we describe, using immunocytochemistry, the strong expression of Vps11 in mouse oligodendrocytes and, specifically, its localization with Myelin Associated Glycoprotein (MAG) in the inner tongue of myelin. In longitudinal sections of myelin, it forms a bead-like structure, alternating with Myelin Basic Protein (MBP). Immunofluorescent staining with Vps11 and neurofilament proteins indicates the absence of Vps11 in axons in vivo. Finally, changes in Vps11 expression are associated with altered proteolipid protein (PLP) levels based upon mice with duplications or deletions of the Plp1 gene. To determine potential functional contributions of Vps11, we combined Vps11 with Platelet Derived Growth Factor Receptor-α (PDGFRα) in vitro and in vivo: in both conditions, co-localization of the two proteins was frequently found in round vesicles of OPCs/oligodendrocytes, suggesting retrograde transport for degradation by the endolysosomal system. Neuron-to-glial communication has been invoked to explain degenerative changes in myelin followed by degenerative changes in axons, and vice versa; but to our knowledge, no specific proteins in retrograde transport from the myelin inner tongue to oligodendrocyte perikarya have been identified. The identification of mutations in VPS11 and its localization at the axon-myelin interface should open new avenues of research.

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空泡蛋白分选11 (Vps11)在哺乳动物少突胶质细胞中的表达
人类VPS11(液泡蛋白分选11)的始创突变最近与德系犹太人的遗传性白质脑病有关,这种病表现为中枢神经系统(CNS)白质紊乱的典型特征。神经功能缺陷包括髓鞘发育减退、张力减退、逐渐丧失视力和癫痫发作。然而,表达突变的细胞没有被鉴定出来。在这里,我们用免疫细胞化学描述了Vps11在小鼠少突胶质细胞中的强表达,特别是它与髓鞘内舌髓鞘相关糖蛋白(MAG)的定位。在髓磷脂的纵剖面中,它形成一个珠状结构,与髓鞘碱性蛋白(MBP)交替。Vps11和神经丝蛋白免疫荧光染色表明体内轴突缺乏Vps11。最后,基于Plp1基因复制或缺失的小鼠,Vps11表达的变化与蛋白脂蛋白(PLP)水平的改变有关。为了确定Vps11的潜在功能贡献,我们在体外和体内将Vps11与血小板衍生生长因子受体-α (PDGFRα)联合使用:在这两种情况下,在OPCs/少突胶质细胞的圆形囊泡中经常发现这两种蛋白的共定位,表明通过内溶酶体系统进行逆行运输降解。神经元与神经胶质之间的通讯被用来解释髓磷脂的退行性变化,随后是轴突的退行性变化,反之亦然;但据我们所知,尚未发现从髓鞘内舌向核周少突胶质细胞逆行运输的特定蛋白。VPS11突变的鉴定及其在轴突-髓鞘界面的定位将开辟新的研究途径。
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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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