Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA.
Nat Cell Biol. 2011 Jan;13(1):40-8. doi: 10.1038/ncb2132. Epub 2010 Dec 12.
Extension of the endoplasmic reticulum (ER) into dendritic spines of Purkinje neurons is required for cerebellar synaptic plasticity and is disrupted in animals with null mutations in Myo5a, the gene encoding myosin-Va. We show here that myosin-Va acts as a point-to-point organelle transporter to pull ER as cargo into Purkinje neuron spines. Specifically, myosin-Va accumulates at the ER tip as the organelle moves into spines, and hydrolysis of ATP by myosin-Va is required for spine ER targeting. Moreover, myosin-Va is responsible for almost all of the spine ER insertion events. Finally, attenuation of the ability of myosin-Va to move along actin filaments reduces the maximum velocity of ER movement into spines, providing direct evidence that myosin-Va drives ER motility. Thus, we have established that an actin-based motor moves ER within animal cells, and have uncovered the mechanism for ER localization to Purkinje neuron spines, a prerequisite for synaptic plasticity.
内质网（ER）向浦肯野神经元树突棘的延伸是小脑突触可塑性所必需的，而在肌球蛋白-Va 基因缺失的动物中，这种延伸会被破坏。我们在这里表明，肌球蛋白-Va 作为一种点对点的细胞器转运蛋白，将 ER 作为货物拉进浦肯野神经元的树突棘。具体来说，当细胞器进入树突棘时，肌球蛋白-Va 聚集在 ER 的末端，并且肌球蛋白-Va 的 ATP 水解对于 ER 靶向树突棘是必需的。此外，肌球蛋白-Va 负责几乎所有的树突棘 ER 插入事件。最后，减弱肌球蛋白-Va 沿肌动蛋白丝运动的能力会降低 ER 进入树突棘的最大速度，这为肌球蛋白-Va 驱动 ER 运动提供了直接证据。因此，我们已经确定了一种基于肌动蛋白的马达在动物细胞内移动 ER，并揭示了 ER 定位于浦肯野神经元树突棘的机制，这是突触可塑性的前提。
