Department of Cell Biology and Neurology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Neurosci. 2011 Jul 13;31(28):10228-33. doi: 10.1523/JNEUROSCI.0115-11.2011.
Dendritic spines serve as the postsynaptic platform for most excitatory synapses in the mammalian brain, and their shape and size are tightly correlated with synaptic strength. The actin cytoskeleton plays a crucial role in the spine structure and its modifications during synapse development and plasticity, but the underlying regulatory mechanisms remain to be elucidated. Here, we report that actin capping protein (CP), a regulator of actin filament growth, plays an essential role for spine development and synapse formation. We found that CP expression in rat hippocampus is elevated at and after the stage of substantial synapse formation. CP knockdown in hippocampal cultures resulted in a marked decline in spine density accompanied by increased filopodia-like protrusions. Moreover, the spines of CP knockdown neurons exhibited an altered morphology, highlighted by multiple thin filopodia-like protrusions emerging from the spine head. Finally, the number of functional synapses was reduced by CP knockdown as evidenced by a reduction in the density of paired presynaptic and postsynaptic markers and in the frequency of miniature EPSCs. These findings indicate that capping of actin filaments by CP represents an essential step for the remodeling of the actin architecture underlying spine morphogenesis and synaptic formation during development.
树突棘作为哺乳动物大脑中大多数兴奋性突触的后突触平台,其形状和大小与突触强度密切相关。肌动蛋白细胞骨架在突触发育和可塑性过程中的棘突结构及其修饰中起着至关重要的作用,但潜在的调节机制仍有待阐明。在这里,我们报告肌动蛋白加帽蛋白(CP),一种肌动蛋白丝生长的调节剂,在大量突触形成时和之后在大鼠海马体中的表达上调。在海马体培养物中敲低 CP 会导致棘突密度显著下降,同时伴有丝状伪足样突起增加。此外,CP 敲低神经元的棘突表现出改变的形态,突出的特征是从棘突头部出现多个细的丝状伪足样突起。最后,CP 敲低导致功能性突触数量减少,这表现在突触前和突触后标志物密度降低以及微小 EPSC 频率降低。这些发现表明,CP 对肌动蛋白丝的加帽代表了在发育过程中棘突形态发生和突触形成的肌动蛋白结构重塑的一个重要步骤。