Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1.
Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1.
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DOI：
10.1038/srep35497
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发表时间：
2016-10-20
影响因子：
4.6
通讯作者：
Conant K
中科院分区：
文献类型：
--
作者：
Allen M;Ghosh S;Ahern GP;Villapol S;Maguire-Zeiss KA;Conant K
基质金属蛋白酶 (MMP) 是由神经元和神经胶质细胞表达的分泌性内肽酶家族。调节的 MMP 活性有助于生理突触可塑性，而失调的活性会刺激损伤。由于结构和功能的重叠以及细胞类型的特异性表达，很难弄清楚单个 MMP 在突触可塑性中所起的作用。在这里，我们开发了一种新的系统来研究体内由 GFAP 表达细胞驱动的单个 MMP 的选择性过表达。我们发现，MMP-1 诱导的细胞和行为表型与通过 G 蛋白偶联蛋白酶激活受体 1 (PAR1) 增强的信号传导一致。体外应用外源性 MMP-1 可刺激 PAR1 依赖性细胞内 Ca2+ 浓度和树突状树枝化的增加。 MMP-1 在体内的过度表达会增加树突的复杂性，并诱导与 GPCR 信号传导增强一致的生化和行为终点。这些数据令人兴奋，因为我们证明星形胶质细胞衍生的蛋白酶可以通过细胞外基质独立机制影响神经元可塑性。
Matrix metalloproteinases (MMPs) are a family of secreted endopeptidases expressed by neurons and glia. Regulated MMP activity contributes to physiological synaptic plasticity, while dysregulated activity can stimulate injury. Disentangling the role individual MMPs play in synaptic plasticity is difficult due to overlapping structure and function as well as cell-type specific expression. Here, we develop a novel system to investigate the selective overexpression of a single MMP driven by GFAP expressing cells in vivo. We show that MMP-1 induces cellular and behavioral phenotypes consistent with enhanced signaling through the G-protein coupled protease activated receptor 1 (PAR1). Application of exogenous MMP-1, in vitro, stimulates PAR1 dependent increases in intracellular Ca2+ concentration and dendritic arborization. Overexpression of MMP-1, in vivo, increases dendritic complexity and induces biochemical and behavioral endpoints consistent with increased GPCR signaling. These data are exciting because we demonstrate that an astrocyte-derived protease can influence neuronal plasticity through an extracellular matrix independent mechanism.
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影响因子：
3.1
作者：
Aerts, Jeroen;Nys, Julie;Arckens, Lutgarde
通讯作者：
Arckens, Lutgarde
影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
DOI：
10.1165/rcmb.2007-0386oc
发表时间：
2009-12-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
7.2
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
Kuliopulos, A