BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions.
BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions.
复制标题
DOI：
10.1523/jneurosci.2445-11.2011
复制
发表时间：
2011-10-26
期刊：
影响因子：
--
通讯作者：
Dent EW
中科院分区：
文献类型：
--
作者：
Hu X;Ballo L;Pietila L;Viesselmann C;Ballweg J;Lumbard D;Stevenson M;Merriam E;Dent EW
微管（MT）能够通过动态聚合进入成熟海马神经元的树突棘。虽然这些MT入侵与神经元活动直接相关，但其功能仍然未知。在这里，我们证明在小鼠海马神经元，MT进入脊髓调节突触后密度蛋白-95（PSD-95）的增加后，脑源性神经营养因子（BDNF）治疗。使用多波长全内反射荧光显微镜（TIRFM），我们发现，BDNF延长MT在脊髓中的平均停留时间，这种效果依赖于TrkB受体激活。进一步的检查显示MT聚合到棘中的峰对应于棘头部中PSD-95的快速增加。随着时间的推移，在BDNF应用后而不是之前，MT靶向的棘显示PSD-95的稳健增加。相反，完全没有MT侵袭的脊柱显示PSD-95水平没有显著变化。MT动力学的药理学抑制消除了BDNF诱导的PSD-95增加。总之，这些结果支持了这样的假设，即BDNF处理后脊髓内PSD-95的众所周知的增加依赖于树突棘的MT侵入。因此，我们的研究提供了一个直接的联系动态MT和突触后结构，并提供了一个功能的作用MT入侵树突棘。
Microtubules (MTs) are capable of entering dendritic spines in mature hippocampal neurons through dynamic polymerization. Although these MT invasions are directly associated with neuronal activity, their function remains unknown. Here we demonstrate in mouse hippocampal neurons that MT entries into spines regulate the increase in post-synaptic density protein-95 (PSD-95) after brain-derived neurotrophic factor (BDNF) treatment. Using multi-wavelength total internal reflectance fluorescence microscopy (TIRFM) we show that BDNF prolonged the average MT dwell time in spines and this effect was dependent on TrkB receptor activation. Further examination revealed that peaks of MT polymerization into spines corresponded to rapid PSD-95 increases in the spine head. Over time, spines targeted by MTs after BDNF application, but not before, showed a robust increase in PSD-95. Conversely, spines completely devoid of MT invasions showed no significant change in the level of PSD-95. Pharmacological inhibition of MT dynamics abolished the BDNF-induced increase in PSD-95. Together these results support the hypothesis that the well known increase in PSD-95 within spines after BDNF treatment is dependent on MT invasions of dendritic spines. Thus, our study provides a direct link between dynamic MTs and the post-synaptic structure, and provides a functional role for MT invasion of dendritic spines.