Liu An, Zhou Zikai, Dang Rui, Zhu Yuehua, Qi Junxia, He Guiqin, Leung Celeste, Pak Daniel, Jia Zhengping, Xie Wei
The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China.
J Cell Biol. 2016 Feb 15;212(4):449-63. doi: 10.1083/jcb.201509023.
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.
神经连接蛋白（NLG）1对突触的发育和功能很重要，但其潜在机制仍不清楚。已知NLG1功能的至少某些方面独立于突触前的神经连接素，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会经历活性依赖的蛋白水解切割，产生一个胞质CTD片段，但这一过程的意义仍不清楚。在本研究中，我们表明NLG1的CTD足以（a）增加树突棘和突触数量，（b）调节突触可塑性，以及（c）通过其与树突棘相关的Rap鸟苷三磷酸酶激活蛋白相互作用并随后激活LIM结构域蛋白激酶1/丝切蛋白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，通过该机制NLG1调节突触发育和功能。
