Steiner Pascal, Higley Michael J, Xu Weifeng, Czervionke Brian L, Malenka Robert C, Sabatini Bernardo L
Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Neuron. 2008 Dec 10;60(5):788-802. doi: 10.1016/j.neuron.2008.10.014.
Long-term potentiation (LTP) is accompanied by dendritic spine growth and changes in the composition of the postsynaptic density (PSD). We find that activity-dependent growth of apical spines of CA1 pyramidal neurons is accompanied by destabilization of the PSD that results in transient loss and rapid replacement of PSD-95 and SHANK2. Signaling through PSD-95 is required for activity-dependent spine growth and trafficking of SHANK2. N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD-95 coordinates multiple signals to regulate morphological plasticity. Activity-dependent trafficking of PSD-95 is triggered by phosphorylation at serine 73, a conserved calcium/calmodulin-dependent protein kinase II (CaMKII) consensus phosphorylation site, which negatively regulates spine growth and potentiation of synaptic currents. We propose that PSD-95 and CaMKII act at multiple steps during plasticity induction to initially trigger and later terminate spine growth by trafficking growth-promoting PSD proteins out of the active spine.
长时程增强（LTP）伴随着树突棘的生长以及突触后致密区（PSD）组成的变化。我们发现，CA1锥体神经元顶端棘的活性依赖生长伴随着PSD的不稳定，这导致PSD-95和SHANK2的短暂丢失及快速替换。活性依赖的棘生长以及SHANK2的转运需要通过PSD-95进行信号传导。PSD-95的N端PDZ结构域和C端鸟苷酸激酶结构域对于这两个过程均是必需的，这表明PSD-95协调多种信号以调节形态可塑性。PSD-95的活性依赖转运由丝氨酸73处的磷酸化触发，丝氨酸73是一个保守的钙/钙调蛋白依赖性蛋白激酶II（CaMKII）共有磷酸化位点，该位点负向调节棘生长和突触电流增强。我们提出，PSD-�5和CaMKII在可塑性诱导的多个步骤中发挥作用，最初通过将促进生长的PSD蛋白转运出活跃的棘来触发并随后终止棘生长。
