Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines
Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines
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DOI：
10.1016/j.neuron.2007.10.005
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发表时间：
2007-11-21
期刊：
影响因子：
16.2
通讯作者：
Penzes, Peter
中科院分区：
文献类型：
--
作者：
Xie, Zhong;Srivastava, Deepak P.;Penzes, Peter
中枢兴奋性突触的活动依赖性快速结构和功能修饰有助于突触成熟、经验依赖性可塑性以及学习和记忆，并与神经发育和精神疾病相关。然而，将谷氨酸受体激活与实现结构和功能可塑性的细胞内效应器联系起来的信号转导机制尚不清楚。在此，我们报道锥体神经元中的 NMDA 受体激活导致鸟嘌呤核苷酸交换因子 (GEF) kalirin-7 在苏氨酸 95 残基处发生 CaMKII 依赖性磷酸化，调节其 GEF 活性，导致小 GTPase Rac1 的激活和现有棘的快速增大。 Kalirin-7 还与 AMPA 受体相互作用并控制其突触表达。通过证明 Kalirin 表达和脊柱定位是活动依赖性脊柱扩大和 AMPAR 介导的突触传递增强所必需的，我们的研究确定了控制结构和功能脊柱可塑性的信号通路。
Activity-dependent rapid structural and functional modifications of central excitatory synapses contribute to synapse maturation, experience-dependent plasticity, and learning and memory and are associated with neuro-developmental and psychiatric disorders. However, the signal transduction mechanisms that link glutamate receptor activation to intracellular effectors that accomplish structural and functional plasticity are not well understood. Here we report that NMDA receptor activation in pyramidal neurons causes CaMKII-dependent phosphorylation of the guanine-nucleotide exchange factor (GEF) kalirin-7 at residue threonine 95, regulating its GEF activity, leading to activation of small GTPase Rac1 and rapid enlargement of existing spines. Kalirin-7 also interacts with AMPA receptors and controls their synaptic expression. By demonstrating that kalirin expression and spine localization are required for activity-dependent spine enlargement and enhancement of AMPAR-mediated synaptic transmission, our study identifies a signaling pathway that controls structural and functional spine plasticity.