Ermin, a myelinating oligodendrocyte-specific protein that regulates cell morphology
Ermin, a myelinating oligodendrocyte-specific protein that regulates cell morphology
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DOI：
10.1523/jneurosci.4317-05.2006
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发表时间：
2006-01-18
影响因子：
5.3
通讯作者：
Peles, E
中科院分区：
文献类型：
--
作者：
Brockschnieder, D;Sabanay, H;Peles, E
少突胶质细胞在轴突周围形成致密髓鞘的绝缘多层结构，从而允许动作电位的快速传播。尽管髓鞘形成具有相当大的临床重要性，但人们对少突胶质细胞产生专门的膜包裹的分子机制知之甚少。在这里，我们使用微阵列表达谱的少突胶质细胞消融突变小鼠，以确定新的神经胶质分子参与中枢神经系统髓鞘形成。这一努力导致Ermin的鉴定，Ermin是一种仅由少突胶质细胞表达的新型细胞骨架分子。Ermin出现在髓鞘形成的晚期，在成熟的神经中，它定位于髓鞘的外细胞质唇和结旁环。在培养的少突胶质细胞中，Ermin在分化良好的MBP阳性细胞中变得可见，在那里它集中在富含F-肌动蛋白的过程的尖端（称为“Ermin尖峰”）。Ermin的异位表达，但不是缺乏肌动蛋白结合域的突变蛋白，诱导形成许多细胞突起和细胞形态的显着变化。我们的研究结果表明，Ermin是一种新的标记髓鞘少突胶质细胞，并建议它发挥了作用，在后期包装和/或压缩阶段的髓鞘细胞骨架重排。
Oligodendrocytes form an insulating multilamellar structure of compact myelin around axons, thereby allowing rapid propagation of action potentials. Despite the considerable clinical importance of myelination, little is known about the molecular mechanisms that enable oligodendrocytes to generate their specialized membrane wrapping. Here, we used microarray expression profiling of oligodendrocyte-ablated mutant mice to identify new glial molecules that are involved in CNS myelination. This effort resulted in the identification of Ermin, a novel cytoskeletal molecule that is exclusively expressed by oligodendrocytes. Ermin appears at a late stage during myelination, and in the mature nerves, it is localized to the outer cytoplasmic lip of the myelin sheath and the paranodal loops. In cultured oligodendrocytes, Ermin becomes visible in well differentiated MBP-positive cells, where it is concentrated at the tip of F-actin-rich processes ( termed "Ermin spikes"). Ectopic expression of Ermin, but not of a mutant protein lacking its actin-binding domain, induced the formation of numerous cell protrusions and a pronounced change in cell morphology. Our results demonstrate that Ermin is a novel marker of myelinating oligodendroglia and suggest that it plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis.