Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction.
Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction.
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DOI：
10.1038/ncomms6066
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发表时间：
2014-10-09
影响因子：
16.6
通讯作者：
Zacchi, Paola
中科院分区：
文献类型：
--
作者：
Antonelli, Roberta;Pizzarelli, Rocco;Pedroni, Andrea;Fritschy, Jean-Marc;Del Sal, Giannino;Cherubini, Enrico;Zacchi, Paola
细胞粘附分子Neuroligin 2（NL 2）选择性地定位于GABA能突触，在那里它与突触后密度中的支架蛋白桥蛋白相互作用。然而，这种相互作用对GABA能突触的形成和可塑性的作用尚不清楚。在这里，我们证明，内源性NL 2经历脯氨酸定向磷酸化在其独特的S714-P共识网站，导致招聘的肽基脯氨酰顺反异构酶Pin 1。该信号级联负调节NL 2在GABA能突触后位点与桥蛋白相互作用的能力。因此，在Pin 1基因敲除小鼠（Pin 1 −/−）海马中的GABA能突触处检测到NL 2、桥蛋白和GABAA受体的累积增强，这与自发GABAA介导的突触后电流的振幅增加有关。我们的研究结果表明，Pin 1依赖的信号转导代表了一种通过调节NL 2/桥蛋白相互作用来调节GABA能传递的机制。 细胞粘附分子Neuroligin 2（NL 2）与支架蛋白桥蛋白相互作用以确保抑制性突触处GABAA受体的功能组织。在这里，作者表明，NL 2结合Pin 1负调节其与这些突触处的桥蛋白复合的能力。
The cell adhesion molecule Neuroligin2 (NL2) is localized selectively at GABAergic synapses, where it interacts with the scaffolding protein gephyrin in the post-synaptic density. However, the role of this interaction for formation and plasticity of GABAergic synapses is unclear. Here, we demonstrate that endogenous NL2 undergoes proline-directed phosphorylation at its unique S714-P consensus site, leading to the recruitment of the peptidyl-prolyl cis–trans isomerase Pin1. This signalling cascade negatively regulates NL2’s ability to interact with gephyrin at GABAergic post-synaptic sites. As a consequence, enhanced accumulation of NL2, gephyrin and GABAA receptors was detected at GABAergic synapses in the hippocampus of Pin1-knockout mice (Pin1−/−) associated with an increase in amplitude of spontaneous GABAA-mediated post-synaptic currents. Our results suggest that Pin1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NL2/gephyrin interaction. The cell adhesion molecule Neuroligin2 (NL2) interacts with the scaffolding protein gephyrin to ensure the functional organization of GABAA receptors at inhibitory synapses. Here the authors show that NL2 binding of Pin1 negatively regulates its ability to complex with gephyrin at these synapses.
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影响因子：
4.8
作者：
Maric, Hans-Michael;Mukherjee, Jayanta;Schindelin, Hermann
通讯作者：
Schindelin, Hermann
DOI：
10.1073/pnas.80.10.2926
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAVIS, FM;TSAO, TY;RAO, PN
通讯作者：
RAO, PN
影响因子：
16.2
作者：
Poulopoulos, Alexandros;Aramuni, Gayane;Varoqueaux, Frederique
通讯作者：
Varoqueaux, Frederique
影响因子：
25
作者：
Essrich, C;Lorez, M;Lüscher, B
通讯作者：
Lüscher, B
影响因子：
3.4
作者：
Dumoulin, A;Lévi, S;Triller, A
通讯作者：
Triller, A