Zuchero J Bradley, Fu Meng-Meng, Sloan Steven A, Ibrahim Adiljan, Olson Andrew, Zaremba Anita, Dugas Jason C, Wienbar Sophia, Caprariello Andrew V, Kantor Christopher, Leonoudakis Dmitri, Lariosa-Willingham Karen, Kronenberg Golo, Gertz Karen, Soderling Scott H, Miller Robert H, Barres Ben A
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dev Cell. 2015 Jul 27;34(2):152-67. doi: 10.1016/j.devcel.2015.06.011. Epub 2015 Jul 9.
Myelin is essential in vertebrates for the rapid propagation of action potentials, but the molecular mechanisms driving its formation remain largely unknown. Here we show that the initial stage of process extension and axon ensheathment by oligodendrocytes requires dynamic actin filament assembly by the Arp2/3 complex. Unexpectedly, subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins and rapid disassembly of the oligodendrocyte actin cytoskeleton and does not require Arp2/3. Inducing loss of actin filaments drives oligodendrocyte membrane spreading and myelin wrapping in vivo, and the actin disassembly factor gelsolin is required for normal wrapping. We show that myelin basic protein, a protein essential for CNS myelin wrapping whose role has been unclear, is required for actin disassembly, and its loss phenocopies loss of actin disassembly proteins. Together, these findings provide insight into the molecular mechanism of myelin wrapping and identify it as an actin-independent form of mammalian cell motility.
髓磷脂对于脊椎动物动作电位的快速传播至关重要，但其形成的分子机制在很大程度上仍不清楚。在这里，我们表明少突胶质细胞的突起延伸和轴突包裹的初始阶段需要Arp2/3复合物驱动动态肌动蛋白丝组装。出乎意料的是，随后的髓鞘包裹与肌动蛋白解聚蛋白的上调以及少突胶质细胞肌动蛋白细胞骨架的快速解聚同时发生，并且不需要Arp2/3。诱导肌动蛋白丝的丢失会驱动少突胶质细胞膜在体内的铺展和髓鞘包裹，而肌动蛋白解聚因子凝溶胶蛋白是正常包裹所必需的。我们表明，髓鞘碱性蛋白是中枢神经系统髓鞘包裹所必需的一种蛋白质，其作用尚不清楚，它是肌动蛋白解聚所必需的，其缺失模拟了肌动蛋白解聚蛋白的缺失。总之，这些发现为髓鞘包裹的分子机制提供了见解，并将其确定为一种不依赖肌动蛋白的哺乳动物细胞运动形式。
