The E3 Ubiquitin Ligase SYVN1 Ubiquitinates Atlastins to Remodel the Endoplasmic Reticulum Network.

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. SYVN1 overexpression compensates the excessive ER network fusion caused by ATL1 overexpression. Accordingly, the role of SYVN1 and ATL1 in regulating ER morphology is also recapitulated in Caenorhabditis elegans. Taken together, our study reveals a different role of SYVN1 in ER remodeling through mediating ubiquitination on ATLs.