Blanpied Thomas A, Kerr Justin M, Ehlers Michael D
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12587-92. doi: 10.1073/pnas.0711669105. Epub 2008 Aug 22.
The size, shape, and molecular arrangement of the postsynaptic density (PSD) determine the function of excitatory synapses in the brain. Here, we directly measured the internal dynamics of scaffold proteins within single living PSDs, focusing on the principal scaffold protein PSD-95. We found that individual PSDs undergo rapid, continuous changes in morphology driven by the actin cytoskeleton and regulated by synaptic activity. This structural plasticity is accompanied by rapid fluctuations in internal scaffold density over submicron distances. Using targeted photobleaching and photoactivation of PSD subregions, we show that PSD-95 is nearly immobile within the PSD, and PSD subdomains can be maintained over long periods. We propose a flexible matrix model of the PSD based on stable molecular positioning of PSD-95 scaffolds.
突触后致密区(PSD)的大小、形状和分子排列决定了大脑中兴奋性突触的功能。在此,我们直接测量了单个活体PSD内支架蛋白的内部动态变化,重点关注主要支架蛋白PSD-95。我们发现,单个PSD会经历由肌动蛋白细胞骨架驱动并受突触活动调节的快速、持续的形态变化。这种结构可塑性伴随着亚微米距离内内部支架密度的快速波动。通过对PSD亚区域进行靶向光漂白和光激活,我们表明PSD-95在PSD内几乎是固定不动的,并且PSD亚结构域可以长期维持。我们基于PSD-95支架的稳定分子定位提出了一种PSD的灵活矩阵模型。