Neuronal Signal Transduction Group, Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
International Max Planck Research School for Brain and Behavior, Jupiter, FL, USA.
Sci Rep. 2020 Feb 4;10(1):1777. doi: 10.1038/s41598-020-58610-6.
Structural and functional plasticity of dendritic spines is the basis of animal learning. The rapid remodeling of actin cytoskeleton is associated with spine enlargement and shrinkage, which are essential for structural plasticity. The calcium-dependent protein kinase C isoform, PKCα, has been suggested to be critical for this actin-dependent plasticity. However, mechanisms linking PKCα and structural plasticity of spines are unknown. Here, we examine the spatiotemporal activation of actin regulators, including small GTPases Rac1, Cdc42 and Ras, in the presence or absence of PKCα during single-spine structural plasticity. Removal of PKCα expression in the postsynapse attenuated Rac1 activation during structural plasticity without affecting Ras or Cdc42 activity. Moreover, disruption of a PDZ binding domain within PKCα led to impaired Rac1 activation and deficits in structural spine remodeling. These results demonstrate that PKCα positively regulates the activation of Rac1 during structural plasticity.
树突棘的结构和功能可塑性是动物学习的基础。肌动蛋白细胞骨架的快速重塑与棘突的增大和缩小有关，这对于结构可塑性是必不可少的。钙依赖性蛋白激酶 C 同工型 PKCα 被认为对这种依赖于肌动蛋白的可塑性至关重要。然而，PKCα 与棘突结构可塑性之间的联系机制尚不清楚。在这里，我们研究了在单个棘突结构可塑性过程中，PKCα 存在或不存在时，肌动蛋白调节剂（包括小 GTPases Rac1、Cdc42 和 Ras）的时空激活情况。在突触后去除 PKCα 表达会减弱结构可塑性过程中的 Rac1 激活，而不影响 Ras 或 Cdc42 的活性。此外，破坏 PKCα 内的 PDZ 结合域会导致 Rac1 激活受损和结构棘突重塑缺陷。这些结果表明，PKCα 正向调节结构可塑性过程中 Rac1 的激活。
