Zhao Yupeng, Feng Zhigang, Zou Yan, Liu Yanfen
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
iScience. 2020 Aug 24;23(9):101494. doi: 10.1016/j.isci.2020.101494. eCollection 2020 Sep 25.
Atlastin (ATL) is a class of dynamin-like GTPases shaping endoplasmic reticulum (ER) by mediating homotypic membrane fusion. Defect of ATLs leads to abnormal ER structure and hereditary spastic paraplegia (HSP), a neurodegenerative disease with progressive spasticity. How ATLs are regulated to maintain the ER dynamics is not clear. Here, we found that SYVN1, an E3 ubiquitin ligase on the ER membrane, regulates ER shape and COPII exporting by mediating ubiquitination on ATLs, especially ATL1. ATL1 is ubiquitinated by SYVN1 strongly on K285 and mildly on K287. Ubiquitination on ATL1 does not result in protein degradation but inhibits ATL1 GTPase activity. overexpression compensates the excessive ER network fusion caused by overexpression. Accordingly, the role of SYVN1 and ATL1 in regulating ER morphology is also recapitulated in . Taken together, our study reveals a different role of SYVN1 in ER remodeling through mediating ubiquitination on ATLs.
Atlastin（ATL）是一类动力蛋白样GTP酶，通过介导同型膜融合来塑造内质网（ER）。ATL的缺陷会导致内质网结构异常以及遗传性痉挛性截瘫（HSP），这是一种伴有进行性痉挛的神经退行性疾病。目前尚不清楚ATL如何被调控以维持内质网的动态变化。在此，我们发现内质网膜上的E3泛素连接酶SYVN1通过介导ATL尤其是ATL1的泛素化来调节内质网形态和COPII输出。ATL1在K285位点被SYVN1强烈泛素化，在K287位点被轻度泛素化。ATL1的泛素化不会导致蛋白质降解，但会抑制ATL1的GTP酶活性。过表达可补偿由过表达引起的过度内质网网络融合。因此，SYVN1和ATL1在调节内质网形态中的作用也在[具体内容]中得到了重现。综上所述，我们的研究揭示了SYVN1通过介导ATL的泛素化在内质网重塑中的不同作用。
