Xie Zhong, Srivastava Deepak P, Photowala Huzefa, Kai Li, Cahill Michael E, Woolfrey Kevin M, Shum Cassandra Y, Surmeier D James, Penzes Peter
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Neuron. 2007 Nov 21;56(4):640-56. doi: 10.1016/j.neuron.2007.10.005.
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 neurodevelopmental 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.
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未完全清楚。在此，我们报告锥体细胞中的NMDA受体激活会导致鸟嘌呤核苷酸交换因子（GEF）kalirin-7的苏氨酸95位点发生CaMKII依赖性磷酸化，调节其GEF活性，从而导致小GTP酶Rac1的激活以及现有棘突的快速增大。Kalirin-7还与AMPA受体相互作用并控制其突触表达。通过证明kalirin的表达和棘突定位是活动依赖性棘突增大和AMPA受体介导的突触传递增强所必需的，我们的研究确定了一条控制棘突结构和功能可塑性的信号通路。
