Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila.
Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila.
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果蝇中功能性 Neuroligin 2 的成熟和运输需要蛋白水解裂解。
DOI：
10.1093/jmcb/mjx015
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发表时间：
2017-06-01
影响因子：
5.5
通讯作者：
Xie W
中科院分区：
文献类型：
--
作者：
Tu R;Qian J;Rui M;Tao N;Sun M;Zhuang Y;Lv H;Han J;Li M;Xie W
Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642−T698 is required for this process. The immature non-cleavable DNlg2 is retained in the ER and non-functional. The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNlg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNlg2 leads to similar marked defects in DNlg2 proteolytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our findings uncover a specific mechanism that controls DNlg2 maturation and trafficking via proteolytic cleavage in the ER, suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to autism disorder.
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影响因子：
4.8
作者：
Lin, HH;Chang, GW;Gordon, S
通讯作者：
Gordon, S
影响因子：
11.4
作者：
Ko, Jaewon;Zhang, Chen;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
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
发表时间：
2016-02-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Liu A;Zhou Z;Dang R;Zhu Y;Qi J;He G;Leung C;Pak D;Jia Z;Xie W
通讯作者：
Xie W
影响因子：
16.2
作者：
Banovic, Daniel;Khorramshahi, Omid;Aberle, Hermann
通讯作者：
Aberle, Hermann
影响因子：
5.3
作者：
Comoletti, D;De Jaco, A;Taylor, P
通讯作者：
Taylor, P