Koskinen Mikko, Bertling Enni, Hotulainen Risto, Tanhuanpää Kimmo, Hotulainen Pirta
Neuroscience Center, Viikinkaari 4, 00014 University of Helsinki, Finland.
Special Education, Siltavuorenpenger 3 A, 00014 University of Helsinki, Finland.
Mol Cell Neurosci. 2014 Jul;61:56-64. doi: 10.1016/j.mcn.2014.05.008. Epub 2014 Jun 3.
Precise control of the formation and development of dendritic spines is critical for synaptic plasticity. Consequently, abnormal spine development is linked to various neurological disorders. The actin cytoskeleton is a structural element generating specific changes in dendritic spine morphology. Although mechanisms underlying dendritic filopodia elongation and spine head growth are relatively well understood, it is still not known how spine heads are enlarged and stabilized during dendritic spine maturation. By using rat hippocampal neurons, we demonstrate that the size of the stable actin pool increases during the neuronal maturation process. Simultaneously, the treadmilling rate of the dynamic actin pool increases. We further show that myosin IIb controls dendritic spine actin cytoskeleton by regulating these two different pools of F-actin via distinct mechanisms. The findings indicate that myosin IIb stabilizes the stable F-actin pool through actin cross-linking. Simultaneously, activation of myosin IIb contractility increases the treadmilling rate of the dynamic pool of actin. Collectively, these data show that myosin IIb has a major role in the regulation of actin filament stability in dendritic spines, and elucidate the complex mechanism through which myosin IIb functions in this process. These new insights into the mechanisms underlying dendritic spine maturation further the model of dendritic spine morphogenesis.
精确控制树突棘的形成和发育对于突触可塑性至关重要。因此，异常的树突棘发育与多种神经疾病相关。肌动蛋白细胞骨架是一种在树突棘形态上产生特定变化的结构元件。尽管对树突丝状伪足伸长和棘头生长的潜在机制已有较好理解，但树突棘成熟过程中棘头如何增大和稳定仍不清楚。通过使用大鼠海马神经元，我们证明在神经元成熟过程中稳定肌动蛋白池的大小增加。同时，动态肌动蛋白池的踏车速率增加。我们进一步表明，肌球蛋白IIb通过不同机制调节这两个不同的F-肌动蛋白池来控制树突棘肌动蛋白细胞骨架。研究结果表明，肌球蛋白IIb通过肌动蛋白交联稳定稳定的F-肌动蛋白池。同时，肌球蛋白IIb收缩性的激活增加了动态肌动蛋白池的踏车速率。总体而言，这些数据表明肌球蛋白IIb在调节树突棘中肌动蛋白丝稳定性方面起主要作用，并阐明了肌球蛋白IIb在此过程中发挥作用的复杂机制。这些对树突棘成熟潜在机制的新见解进一步完善了树突棘形态发生模型。
