生物谷報道：面對慢性的各級神經(jīng)網(wǎng)絡(luò)活動的變化，動態(tài)平衡的神經(jīng)突觸可塑性保證了神經(jīng)元細胞在最優(yōu)范圍內(nèi)輸出最佳信號,。然而,，這種現(xiàn)象背后的分子機制人們知之甚少，特別是對于活性增高的回應(yīng)機制還不為人所知,。
在5月22日的《神經(jīng)元》（Neuron）上,，美國研究人員指出，在海馬神經(jīng)元活性增高的過程中,，誘導(dǎo)蛋白激酶Polo樣激酶2（Plk2,，也稱SNK）的突觸放大的主要機制是動態(tài)平衡的神經(jīng)突觸可塑性。神經(jīng)突觸的縮放尺度還需要CDK5,，CDK5在磷酸依賴型Plk2與其底物SPAR的結(jié)合過程中充當著“啟動”激酶的作用,。SPAR是一個突觸后的RAPgap 和骨架分子，它在Plk2磷酸化后降解,。SPAR的RNA干擾抑制作用削弱了突觸的形成,，SPAR突變體的過度表達對plk2依賴型的抑制阻止了突觸的縮放尺度。
因此,，在SPAR中,，由CDK5引發(fā)的Plk2結(jié)合位點的啟動磷酸化，以及隨后補充的Plk2和SPAR磷酸化降解過程,，共同構(gòu)成了慢性活性增高的神經(jīng)元動態(tài)平衡可塑性的分子途徑,。（生物谷www.bioon.com）
生物谷推薦原始出處：
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.
