Zhu Jing, Xie Ruize, Ren Qiaoying, Zhou Jiaming, Chen Chen, Xie Meng-Xi, Zhou You, Zhang Yan, Liu Ningjing, Wang Jinchao, Zhang Zhengwei, Liu Xipeng, Yan Wupeng, Gong Qingqiu, Dong Liang, Zhu Jinwei, Wang Fengping, Xie Zhiping
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, PR China.
Nat Commun. 2025 Mar 17;16(1):2622. doi: 10.1038/s41467-025-57902-7.
Inward membrane budding, i.e., the bending of membrane towards the cytosol, is essential for forming and maintaining eukaryotic organelles. In eukaryotes, Arf GTPases initiate this inward budding. Our research shows that Asgard archaea genomes encode putative Arf proteins (AArfs). AArfs possess structural elements characteristic of their eukaryotic counterparts. When expressed in yeast and mammalian cells, some AArfs displayed GTP-dependent membrane targeting. In vitro, AArf associated with both eukaryotic and archaeal membranes. In yeast, AArfs interacted with and were regulated by key organelle biogenesis players. Expressing an AArf led to a massive proliferation of endomembrane organelles including the endoplasmic reticulum and Golgi. This AArf interacted with Sec23, a COPII vesicle coat component, in a GTP-dependent manner. These findings suggest certain AArfs are membrane-associating molecular switches with the functional potential to initiate organelle biogenesis, and the evolution of a functional coat could be the next critical step towards establishing eukaryotic cell architecture.
内膜出芽，即膜向细胞质溶胶弯曲，对于真核细胞器的形成和维持至关重要。在真核生物中，Arf GTP酶启动这种向内出芽。我们的研究表明，阿斯加德古菌基因组编码假定的Arf蛋白（AArfs）。AArfs具有与其真核对应物相同的结构元件。当在酵母和哺乳动物细胞中表达时，一些AArfs表现出GTP依赖性的膜靶向性。在体外，AArf与真核和古菌膜都有关联。在酵母中，AArfs与关键的细胞器生物发生因子相互作用并受其调节。表达一种AArf会导致包括内质网和高尔基体在内的内膜细胞器大量增殖。这种AArf以GTP依赖的方式与COPII囊泡衣被成分Sec23相互作用。这些发现表明某些AArfs是具有启动细胞器生物发生功能潜力的膜结合分子开关，而功能性衣被的进化可能是建立真核细胞结构的下一个关键步骤。
