Meng Yanghong, Zhang Yu, Tregoubov Vitali, Falls Douglas L, Jia Zhengping
Program in Brain and Behavior, The Hospital For Sick Children, Toronto, Ontario, Canada.
Rev Neurosci. 2003;14(3):233-40. doi: 10.1515/revneuro.2003.14.3.233.
Filamentous actin (F-actin) is highly enriched in the dendritic spine, a specialized postsynaptic structure on which the great majority of the excitatory synapses are formed in the mammalian central nervous system (CNS). The protein kinases of the Lim-kinase (LIMK) family are potent regulators of actin dynamics in many cell types and they are abundantly expressed in the CNS, including the hippocampus. Using a combination of genetic manipulations and electrophysiological recordings in mice, we have demonstrated that LIMK-1 signaling is important in vivo in the regulation of the actin cytoskeleton, spine morphology, and synaptic function, including hippocampal long-term potentiation (LTP), a prominent form of long lasting synaptic plasticity thought to be critical to memory formation. Our results provide strong genetic evidence that LIMK and its substrate ADF/cofilin are involved in spine morphology and synaptic properties and are consistent with the notion that the Rho family small GTPases and the actin cytoskeleton are critical to spine structure and synaptic regulation.
丝状肌动蛋白（F-肌动蛋白）在树突棘中高度富集，树突棘是一种特殊的突触后结构，在哺乳动物中枢神经系统（CNS）中，绝大多数兴奋性突触都形成于此。Lim激酶（LIMK）家族的蛋白激酶是许多细胞类型中肌动蛋白动力学的有效调节因子，它们在包括海马体在内的中枢神经系统中大量表达。通过在小鼠中结合基因操作和电生理记录，我们已经证明LIMK-1信号在体内对肌动蛋白细胞骨架、棘形态和突触功能的调节中很重要，包括海马体长期增强（LTP），这是一种持久的突触可塑性的突出形式，被认为对记忆形成至关重要。我们的结果提供了强有力的遗传学证据，表明LIMK及其底物ADF/丝切蛋白参与了棘形态和突触特性，并且与Rho家族小GTP酶和肌动蛋白细胞骨架对棘结构和突触调节至关重要的观点一致。
