Atlastin-mediated membrane tethering is critical for cargo mobility and exit from the endoplasmic reticulum
| Autor: | Feng Yang, Tianji Ma, Liling Niu, Bing Yan, Junjie Hu, Haidi Yin, Qian Wu, Jifeng Wang, Yan Huang, Xiao Tang, Zhongping Yao, Yusong Guo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Atlastin
Hereditary spastic paraplegia Golgi Apparatus GTPase Endoplasmic Reticulum medicine.disease_cause membrane tension GTP-Binding Proteins immune system diseases hemic and lymphatic diseases Chlorocebus aethiops medicine Animals Humans atlastin COPII Sequence Deletion Mutation Multidisciplinary Spastic Paraplegia Hereditary COPII formation Tethering Chemistry Endoplasmic reticulum Vesicle Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Biology Biological Sciences medicine.disease Cell biology Protein Transport PNAS Plus COS Cells Mutant Proteins COP-Coated Vesicles protein mobility |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance In the early secretory pathway, newly synthesized proteins undergo folding and modifications and then leave the ER through COPII-coated vesicles. How these processes are coordinated and maintained are important but mostly unclear. We show here that ATL, a GTPase that connects ER tubules, controls ER protein mobility and regulates cargo packaging and coat assembly of COPII vesicles. The tethering and fusion activity by ATL likely maintains tension and other necessary parameters for COPII formation in ER membranes. These findings reveal a role of ER shaping in the early secretory pathway and provide insight into behaviors of ER exportation. Endoplasmic reticulum (ER) membrane junctions are formed by the dynamin-like GTPase atlastin (ATL). Deletion of ATL results in long unbranched ER tubules in cells, and mutation of human ATL1 is linked to hereditary spastic paraplegia. Here, we demonstrate that COPII formation is drastically decreased in the periphery of ATL-deleted cells. ER export of cargo proteins becomes defective; ER exit site initiation is not affected, but many of the sites fail to recruit COPII subunits. The efficiency of cargo packaging into COPII vesicles is significantly reduced in cells lacking ATLs, or when the ER is transiently fragmented. Cargo is less mobile in the ER in the absence of ATL, but the cargo mobility and COPII formation can be restored by ATL R77A, which is capable of tethering, but not fusing, ER tubules. These findings suggest that the generation of ER junctions by ATL plays a critical role in maintaining the necessary mobility of ER contents to allow efficient packaging of cargo proteins into COPII vesicles. |
| Databáze: | OpenAIRE |
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