Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix
Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix
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DOI：
10.1016/j.celrep.2017.05.023
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发表时间：
2017-05-30
期刊：
影响因子：
8.8
通讯作者：
Ponimaskin, Evgeni
中科院分区：
文献类型：
--
作者：
Bijata, Monika;Labus, Josephine;Ponimaskin, Evgeni
与记忆形成相关的突触回路的重新布线与树突棘的形态学变化和细胞外基质（ECM）重塑有关。在这里，我们通过揭示涉及5-羟色胺5-HT 7受体（5-HT 7 R），基质金属蛋白酶9（MMP-9），透明质酸受体CD 44和小GTdR Cdc 42的信号通路，机械地连接这些过程。我们强调了5-HT 7 R和CD 44（确定为MMP-9底物的神经元）之间的物理相互作用，并发现5-HT 7 R刺激增加局部MMP-9的活性，触发树突棘重塑，突触修剪，和损害的长时程增强（LTP）。潜在的分子机制涉及5-HT 7 R介导的MMP-9活化，其导致CD 44裂解，随后是Cdc 42活化。这种相互作用的一个重要生理后果包括神经元生长的增加和树突棘的延长，这可能对复杂的神经元过程（例如，逆转学习和神经元再生）。
Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration).