Okamura Ko, Tanaka Hidekazu, Yagita Yoshiki, Saeki Yoshinaga, Taguchi Akihiko, Hiraoka Yasushi, Zeng Ling-Hui, Colman David R, Miki Naomasa
Department of Pharmacology, Osaka University Medical School, Suita, Japan.
J Cell Biol. 2004 Dec 6;167(5):961-72. doi: 10.1083/jcb.200406030. Epub 2004 Nov 29.
Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone.
神经活动诱导突触前膜和突触后膜的重塑，这些膜通过细胞粘附分子维持其并置状态。其中，N-钙黏蛋白会重新分布，经历依赖于活动的构象变化，并且是突触可塑性所必需的。在这里，我们表明去极化会诱导棘突头部宽度增大，并且钙黏蛋白活性对于这种突触重排至关重要。在海马神经元中用绿色荧光蛋白可视化的树突棘通过AMPA受体的激活而扩展，从而使突触并置区可能扩大。N-钙黏蛋白-维纳斯融合蛋白沿扩展的棘突头部横向分散。N-钙黏蛋白显性负性形式的过表达导致棘突扩展的消除。用细胞松弛素D抑制肌动蛋白聚合消除了棘突扩展。总之，我们的数据表明基于钙黏蛋白的粘附机制与肌动蛋白细胞骨架相结合对于突触并置区的重塑至关重要。
