Laboratório de Neurobiologia do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, CCS. Bloco G, Rio de Janeiro, 21941-902, Brazil.
Laboratório de Bioquímica de Lipídeos e Lipoproteínas, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Cell Mol Neurobiol. 2021 Apr;41(3):525-536. doi: 10.1007/s10571-020-00869-4. Epub 2020 May 15.
Olfactory ensheathing cells (OECs) are specialized glial cells of the olfactory system, believed to play a role in the continuous production of olfactory neurons and ensheathment of their axons. Although OECs are used in therapeutic applications, little is known about the cellular mechanisms underlying their migratory behavior. Recently, we showed that OEC migration is sensitive to ganglioside blockage through A2B5 and Jones antibody in OEC culture. Gangliosides are common components of lipid rafts, where they participate in several cellular mechanisms, including cell migration. Here, we characterized OEC lipid rafts, analyzing the presence of specific proteins and gangliosides that are commonly expressed in motile neural cells, such as young neurons, oligodendrocyte progenitors, and glioma cells. Our results showed that lipid rafts isolated from OECs were enriched in cholesterol, sphingolipids, phosphatidylcholine, caveolin-1, flotillin-1, gangliosides GM1 and 9-O-acetyl GD3, A2B5-recognized gangliosides, CNPase, α-actinin, and β1-integrin. Analysis of the actin cytoskeleton of OECs revealed stress fibers, membrane spikes, ruffled membranes and lamellipodia during cell migration, as well as the distribution of α-actinin in membrane projections. This is the first description of α-actinin and flotillin-1 in lipid rafts isolated from OECs and suggests that, together with β1-integrin and gangliosides, membrane lipid rafts play a role during OEC migration. This study provides new information on the molecular composition of OEC membrane microdomains that can impact on our understanding of the role of OEC lipid rafts under physiological and pathological conditions of the nervous system, including inflammation, hypoxia, aging, neurodegenerative diseases, head trauma, brain tumor, and infection.
嗅鞘细胞(Olfactory ensheathing cells,OECs)是嗅觉系统中的一种特化胶质细胞,被认为在持续产生嗅觉神经元和包绕其轴突方面发挥作用。尽管 OEC 被用于治疗应用,但对于其迁移行为的细胞机制知之甚少。最近,我们表明,OEC 迁移对 OEC 培养物中 A2B5 和 Jones 抗体阻断神经节苷脂敏感。神经节苷脂是脂质筏的常见成分,它们参与包括细胞迁移在内的多种细胞机制。在这里,我们对 OEC 脂质筏进行了特征分析,分析了存在于运动神经元(如年轻神经元、少突胶质细胞前体细胞和神经胶质瘤细胞)中常见的特定蛋白质和神经节苷脂。我们的结果表明,从 OEC 中分离出的脂质筏富含胆固醇、神经鞘脂、磷脂酰胆碱、质膜窖蛋白 1、陷窝蛋白 1、神经节苷脂 GM1 和 9-O-乙酰 GD3、A2B5 识别的神经节苷脂、CNPase、α-辅肌动蛋白和 β1-整合素。对 OEC 细胞骨架的分析显示,在细胞迁移过程中存在应力纤维、质膜刺突、皱褶质膜和片状伪足,以及 α-辅肌动蛋白在质膜突起中的分布。这是首次在 OEC 分离的脂质筏中描述α-辅肌动蛋白和陷窝蛋白 1,并表明膜脂筏与β1-整合素和神经节苷脂一起在 OEC 迁移过程中发挥作用。本研究为 OEC 质膜微区的分子组成提供了新的信息,这可能会影响我们对 OEC 脂质筏在神经系统生理和病理条件(包括炎症、缺氧、衰老、神经退行性疾病、头部创伤、脑肿瘤和感染)下作用的理解。