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.

人类VPS11的创始人突变（液泡蛋白分选 11）最近被认为与德系犹太人的一种遗传性白质脑病有关，这种病具有中枢神经系统（CNS）白质疾病的典型特征。神经系统缺陷包括髓鞘形成不足、张力减退、视力逐渐丧失和癫痫发作。然而，表达突变的细胞尚未被识别。在这里，我们使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，特别是它与髓磷脂相关糖蛋白（MAG）在髓磷脂内舌中的定位。在髓磷脂的纵向切片中，它形成珠状结构，与髓磷脂碱性蛋白（MBP）交替。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，基于Plp1基因重复或缺失的小鼠，Vps11 表达的变化与蛋白脂质蛋白 (PLP) 水平的改变相关。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) 结合起来：在这两种情况下，两种蛋白质的共定位经常出现在 OPCs/少突胶质细胞的圆形囊泡中，表明内溶酶体系统进行逆行转运以进行降解。神经元与神经胶质的通讯已被用来解释髓磷脂的退行性变化以及轴突的退行性变化，反之亦然；但据我们所知，尚未鉴定出从髓磷脂内舌逆行转运至少突胶质细胞周核的特定蛋白质。VPS11突变的鉴定及其在轴突-髓磷脂界面的定位应该会开辟新的研究途径。