Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes.
Characterization of the Expression of Vacuolar Protein Sorting 11 (Vps11) in Mammalian Oligodendrocytes.
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哺乳动物少突胶质细胞中液泡蛋白分选11（VPS11）的表达的表征。
DOI：
10.1177/17590914211009851
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发表时间：
2021-01
期刊：
影响因子：
4.7
通讯作者：
Thummel R
中科院分区：
文献类型：
--
作者：
Skoff RP;Bessert D;Banerjee S;Luo X;Thummel R
最近，人类VPS11(空泡蛋白分类11)的创始人突变与德系犹太人的一种遗传性白质脑病有关，这种白质脑病呈现出中枢神经系统(CNS)白质障碍的典型特征。神经功能障碍包括髓鞘过少、肌张力降低、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的方法，描述了Vps11在小鼠少突胶质细胞中的强烈表达，特别是它与髓鞘相关糖蛋白(MAG)在髓鞘内舌中的定位。在髓鞘的纵切面上，它与髓鞘碱性蛋白(MBP)交替形成珠状结构。Vps11和神经丝蛋白的免疫荧光染色表明，体内轴突中不存在Vps11。最后，Vps11表达的变化与蛋白脂蛋白(PLP)水平的变化有关，这是基于Plp1基因重复或缺失的小鼠。为了确定VPS11的潜在功能贡献，我们在体内外将VPS11与血小板衍生生长因子受体α(PDGFRα)结合：在这两种情况下，OPC/少突胶质细胞的圆形小泡中经常发现这两种蛋白的共同定位，这表明这两种蛋白的逆行运输导致了内溶体系统的降解。神经元到神经胶质细胞的通讯被用来解释髓鞘的退行性变化和轴突的退行性变化；但据我们所知，还没有鉴定出从髓鞘内舌到少突胶质细胞核周的逆行运输的特定蛋白质。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。
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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DOI：
10.1534/g3.118.200376
发表时间：
2018-07-31
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Lucot KL;Dickinson PJ;Finno CJ;Mansour TA;Letko A;Minor KM;Mickelson JR;Drögemüller C;Brown CT;Bannasch DL
通讯作者：
Bannasch DL
影响因子：
4.7
作者：
Matsumoto, Naoto;Miyamoto, Yuki;Yamauchi, Junji
通讯作者：
Yamauchi, Junji
影响因子：
16.2
作者：
READHEAD, C;SCHNEIDER, A;NAVE, KA
通讯作者：
NAVE, KA
影响因子：
6.2
作者：
Appikatla S;Bessert D;Lee I;Hüttemann M;Mullins C;Somayajulu-Nitu M;Yao F;Skoff RP
通讯作者：
Skoff RP
影响因子：
4
作者：
Edvardson, Shimon;Gerhard, Frank;Elpeleg, Orly
通讯作者：
Elpeleg, Orly