Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system.
Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system.
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DOI：
10.1016/j.devcel.2015.05.013
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发表时间：
2015-07-27
影响因子：
11.8
通讯作者：
Simons M
中科院分区：
文献类型：
--
作者：
Nawaz S;Sánchez P;Schmitt S;Snaidero N;Mitkovski M;Velte C;Brückner BR;Alexopoulos I;Czopka T;Jung SY;Rhee JS;Janshoff A;Witke W;Schaap IAT;Lyons DA;Simons M
在中枢神经系统发育过程中，少突胶质细胞将其质膜包裹在轴突周围以产生多层髓鞘。为了驱动髓鞘在与轴突的界面处的前缘处的生长，机械力是必要的，但潜在的机制尚不清楚。使用一个跨学科的方法，结合形态学，遗传学和生物物理学分析，我们确定了一个关键的作用，肌动蛋白丝网络营业额髓鞘生长。在髓鞘生物发生开始时，F-肌动蛋白被重新分布到前缘，在那里其基于聚合的力推出非粘性和能动的突起。F-肌动蛋白分解通过降低表面张力将突起转化为片材，进而诱导膜铺展和粘附。我们确定了肌动蛋白解聚因子ADF/Cofilin 1，它介导高F-肌动蛋白周转率，在这个过程中的重要因素。我们认为，F-肌动蛋白周转是髓鞘包裹的驱动力，通过调节前缘突出和扩散的重复周期。
During central nervous system development, oligodendrocytes wrap their plasma membrane around axons to generate multi-lamellar myelin sheaths. To drive growth at the leading edge of myelin at the interface with the axon, mechanical forces are necessary, but the underlying mechanisms are not known. Using an interdisciplinary approach that combines morphological, genetic and biophysical analyses, we identified a key role for actin filament network turnover in myelin growth. At the onset of myelin biogenesis, F-actin is redistributed to the leading edge, where its polymerization-based forces push out non-adhesive and motile protrusions. F-actin disassembly converts protrusions into sheets by reducing surface tension and in turn inducing membrane spreading and adhesion. We identified the actin depolymerizing factor ADF/Cofilin1, which mediates high F-actin turnover rates, as essential factor in this process. We propose that F-actin turnover is the driving force in myelin wrapping by regulating repetitive cycles of leading edge protrusion and spreading.