Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation

被引:79
作者
Bilousova, TV
Rusakov, DA
Ethell, DW [1 ]
Ethell, IM
机构
[1] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA
[2] UCL, Inst Neurol, London, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
actin cytoskeleton; dendritic spine; hippocampal neuron; matrilysin; metalloproteinase; NMDA receptor;
D O I
10.1111/j.1471-4159.2006.03701.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dendritic spines are protrusions from the dendritic shaft that host most excitatory synapses in the brain. Although they first emerge during neuronal maturation, dendritic spines remain plastic through adulthood, and recent advances in the molecular mechanisms governing spine morphology have shown them to be exquisitely sensitive to changes in the micro-environment. Among the many factors affecting spine morphology are components and regulators of the extracellular matrix (ECM). Modification of the ECM is critical to the repair of injuries throughout the body, including the CNS. Matrix metalloproteinase (MMP)-7/matrilysin is a key regulator of the ECM during pathogen infection, after nerve crush and in encephalitogenic disorders. We have investigated the effects of MMP-7 on dendritic spines in hippocampal neuron cultures and found that it induces the transformation of mature, short mushroom-shaped spines into long, thin filopodia reminiscent of immature spines. These changes were accompanied by a dramatic redistribution of F-actin from spine heads into thick, rope-like structures in the dendritic shaft. Strikingly, MMP-7 effects on dendritic spines were similar to those of NMDA treatment, and both could be blocked by channel-specific antagonists. These findings are the first direct evidence that MMPs can influence the morphology of mature dendritic spines, and hence synaptic stability.
引用
收藏
页码:44 / 56
页数:13
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