PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling.
PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling.
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DOI：
10.1083/jcb.200805132
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Muller D
中科院分区：
文献类型：
--
作者：
Nikonenko I;Boda B;Steen S;Knott G;Welker E;Muller D
突触后致密物95（PSD-95）是突触结构和可塑性的重要调节因子。然而，其对突触形成和组织的贡献仍不清楚。使用电子显微镜，遗传学和药理学相结合的方法，我们发现了PSD-95调节突触发生的新机制。我们发现，PSD-95过表达影响脊柱形态，但也促进了多神经支配的脊柱（MISs）接触多达7个突触前末梢的形成。通过删除PSD-95的PDZ 2结构域来特异性地防止多个接触的形成，所述PDZ 2结构域与一氧化氮（NO）合酶（NOS）相互作用。类似地，PSD-95过表达结合小干扰RNA介导的下调或NOS的药理学阻断阻止轴突分化为静脉曲张和多突触形成。相反，用NO供体或环磷酸鸟苷类似物处理海马切片诱导MIS。NOS阻断还降低了发育中海马培养物的棘和突触密度。这些结果表明，突触后位点，通过NOS-PSD-95相互作用和NO信号，促进与附近轴突的突触形成。
Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ2 domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA–mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS–PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.
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DOI：
10.1073/pnas.0609307104
发表时间：
2007-03-06
影响因子：
11.1
作者：
Ehrlich, Ingrid;Klein, Matthew;Malinow, Roberto
通讯作者：
Malinow, Roberto
影响因子：
16.2
作者：
Holtmaat, AJGD;Trachtenberg, JT;Svoboda, K
通讯作者：
Svoboda, K
影响因子：
16.2
作者：
Gerrow, K;Romorini, S;El-Husseini, A
通讯作者：
El-Husseini, A
影响因子：
16.2
作者：
Bats, Cecile;Groc, Laurent;Choquet, Daniel
通讯作者：
Choquet, Daniel
影响因子：
64.8
作者：
Matsuzaki, M;Honkura, N;Kasai, H
通讯作者：
Kasai, H