PDF(Pubmed)
Abstract：
Ufmylation is implicated in multiple cellular processes, but little is known about its functions and regulation in protein trafficking. Here, we demonstrate that the genetic depletion of core components of the ufmylation cascade, including ubiquitin-fold modifier 1 (UFM1), UFM1 activation enzyme 5, UFM1-specific ligase 1 (UFL1), UFM1-specific protease 2, and UFM1-binding protein 1 (UFBP1) each markedly inhibits the endoplasmic reticulum (ER)-Golgi transport, surface delivery, and recruitment to COPII vesicles of a subset of G protein-coupled receptors (GPCRs) and UFBP1\'s function partially relies on UFM1 conjugation. We also show that UFBP1 and UFL1 interact with GPCRs and UFBP1 localizes at COPII vesicles coated with specific Sec24 isoforms. Furthermore, the UFBP1/UFL1-binding domain identified in the receptors effectively converts non-GPCR protein transport into the ufmylation-dependent pathway. Collectively, these data reveal important functions for the ufmylation system in GPCR recruitment to COPII vesicles, biosynthetic transport, and sorting at ER via UFBP1 ufmylation and interaction directly.
摘要：
Ufmylation涉及多个细胞过程，但是对其在蛋白质运输中的功能和调节知之甚少。这里,我们证明了ufmylation级联的核心成分的遗传消耗，包括泛素折叠修饰剂1(UFM1)，UFM1激活酶5，UFM1特异性连接酶1（UFL1），UFM1特异性蛋白酶2和UFM1结合蛋白1（UFBP1）各自显着抑制内质网（ER）-高尔基体运输，表面输送,一组G蛋白偶联受体（GPCRs）和UFBP1的功能部分依赖于UFM1的结合。我们还显示UFBP1和UFL1与GPCRs相互作用，UFBP1位于涂有特定Sec24同工型的COPII囊泡处。此外，在受体中鉴定的UFBP1/UFL1结合结构域有效地将非GPCR蛋白转运转化为ufmylation依赖性途径。总的来说，这些数据揭示了Ufmylation系统在GPCR募集到COPII囊泡中的重要功能，生物合成运输，并通过UFBP1的ufmylation和直接相互作用在ER分选。
