Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization.
Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization.
复制标题
Neuroligin 1 通过 LIMK1/cofilin 介导的肌动蛋白重组调节棘和突触可塑性
DOI：
10.1083/jcb.201509023
复制
发表时间：
2016-02-15
期刊：
影响因子：
--
通讯作者：
Xie W
中科院分区：
文献类型：
--
作者：
Liu A;Zhou Z;Dang R;Zhu Y;Qi J;He G;Leung C;Pak D;Jia Z;Xie W
NLG1 的 C 端结构域足以增强棘和突触数量并调节突触可塑性，并且它通过与 SPAR 相互作用以及随后激活 LIMK1/cofilin 介导的肌动蛋白重组来发挥这些作用。 Neuroligin (NLG) 1 对于突触发育和功能很重要，但其潜在机制仍不清楚。众所周知，NLG1 功能的至少某些方面独立于突触前神经毒素，这表明 NLG1 的 C 末端结构域 (CTD) 可能足以进行突触调节。此外，NLG1 会受到活性依赖性蛋白水解裂解，产生胞质 CTD 片段，但这一过程的意义仍不清楚。在这项研究中，我们证明NLG1的CTD足以（a）增加棘和突触数量，（b）调节突触可塑性，以及（c）通过其与棘相关的Rap鸟苷三磷酸酶激活蛋白的相互作用以及随后激活LIM结构域蛋白激酶1/cofilin介导的肌动蛋白重组来发挥这些作用。我们的结果提供了一种新的突触后机制，NLG1 通过该机制调节突触发育和功能。
The C-terminal domain of NLG1 is sufficient to enhance spine and synapse number and to modulate synaptic plasticity, and it exerts these effects via its interaction with SPAR and the subsequent activation of LIMK1/cofilin-mediated actin reorganization. Neuroligin (NLG) 1 is important for synapse development and function, but the underlying mechanisms remain unclear. It is known that at least some aspects of NLG1 function are independent of the presynaptic neurexin, suggesting that the C-terminal domain (CTD) of NLG1 may be sufficient for synaptic regulation. In addition, NLG1 is subjected to activity-dependent proteolytic cleavage, generating a cytosolic CTD fragment, but the significance of this process remains unknown. In this study, we show that the CTD of NLG1 is sufficient to (a) enhance spine and synapse number, (b) modulate synaptic plasticity, and (c) exert these effects via its interaction with spine-associated Rap guanosine triphosphatase–activating protein and subsequent activation of LIM-domain protein kinase 1/cofilin–mediated actin reorganization. Our results provide a novel postsynaptic mechanism by which NLG1 regulates synapse development and function.