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Neuron:神经突触可塑性背后的分子机制

来源:生物谷 2008-06-17 13:04

生物谷报道:面对慢性的各级神经网络活动的变化,动态平衡的神经突触可塑性保证了神经元细胞在最优范围内输出最佳信号。然而,这种现象背后的分子机制人们知之甚少,特别是对于活性增高的回应机制还不为人所知。

在5月22日的《神经元》(Neuron)上,美国研究人员指出,在海马神经元活性增高的过程中,诱导蛋白激酶Polo样激酶2(Plk2,也称SNK)的突触放大的主要机制是动态平衡的神经突触可塑性。神经突触的缩放尺度还需要CDK5,CDK5在磷酸依赖型Plk2与其底物SPAR的结合过程中充当着“启动”激酶的作用。SPAR是一个突触后的RAPgap 和骨架分子,它在Plk2磷酸化后降解。SPAR的RNA干扰抑制作用削弱了突触的形成,SPAR突变体的过度表达对plk2依赖型的抑制阻止了突触的缩放尺度。

因此,在SPAR中,由CDK5引发的Plk2结合位点的启动磷酸化,以及随后补充的Plk2和SPAR磷酸化降解过程,共同构成了慢性活性增高的神经元动态平衡可塑性的分子途径。(生物谷www.bioon.com

生物谷推荐原始出处:

Neuron,Vol 58, 571-583, 22 May 2008,Daniel P. Seeburg, Morgan Sheng

Critical Role of CDK5 and Polo-like Kinase 2 in Homeostatic Synaptic Plasticity during Elevated Activity

Daniel P. Seeburg,1 Monica Feliu-Mojer,1 Johanna Gaiottino,1 Daniel T.S. Pak,2 and Morgan Sheng1,

1 The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
2 Department of Pharmacology, Med-Dent C405, Georgetown University, 3900 Reservoir Road NW, Washington, DC 20057, USA

Summary

Homeostatic plasticity keeps neuronal spiking output within an optimal range in the face of chronically altered levels of network activity. Little is known about the underlying molecular mechanisms, particularly in response to elevated activity. We report that, in hippocampal neurons experiencing heightened activity, the activity-inducible protein kinase Polo-like kinase 2 (Plk2, also known as SNK) was required for synaptic scaling—a principal mechanism underlying homeostatic plasticity. Synaptic scaling also required CDK5, which acted as a “priming” kinase for the phospho-dependent binding of Plk2 to its substrate SPAR, a postsynaptic RapGAP and scaffolding molecule that is degraded following phosphorylation by Plk2. RNAi knockdown of SPAR weakened synapses, and overexpression of a SPAR mutant resistant to Plk2-dependent degradation prevented synaptic scaling. Thus, priming phosphorylation of the Plk2 binding site in SPAR by CDK5, followed by Plk2 recruitment and SPAR phosphorylation-degradation, constitutes a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity.

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