School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju, Republic of Korea.
Cell Logistics Research Center, Gwangju Institute of Science and Technology , Gwangju, Republic of Korea.
J Cell Biol. 2023 Apr 3;222(4). doi: 10.1083/jcb.202109090. Epub 2023 Feb 9.
The dynamin-like GTPase atlastin is believed to be the minimal machinery required for homotypic endoplasmic reticulum (ER) membrane fusion, mainly because Drosophila atlastin is sufficient to drive liposome fusion. However, it remains unclear whether mammalian atlastins, including the three human atlastins, are sufficient to induce liposome fusion, raising doubts about their major roles in mammalian cells. Here, we show that all human atlastins are sufficient to induce fusion when reconstituted into liposomes with a lipid composition mimicking that of the ER. Although the fusogenic activity of ATL1, which is predominantly expressed in neuronal cells, was weaker than that of ATL2 or ATL3, the addition of M1-spastin, a neuron-specific factor, markedly increased ATL1-mediated liposome fusion. Although we observed efficient fusion between ER microsomes isolated from cultured, non-neuronal cells that predominantly express ATL2-1, an autoinhibited isoform of ATL2, ATL2-1 failed to support liposome fusion by itself as reported previously, indicating that cellular factors enable ATL2-1 to mediate ER fusion in vivo.
动力蛋白样 GTP 酶 atlastin 被认为是同源内质网 (ER) 膜融合所必需的最小机制，主要是因为果蝇 atlastin 足以驱动脂质体融合。然而，哺乳动物的 atlastin 是否足以诱导脂质体融合仍不清楚，这让人对其在哺乳动物细胞中的主要作用产生了怀疑。在这里，我们表明，当用模拟 ER 脂质组成的脂质体重新构成时，所有人类的 atlastin 都足以诱导融合。虽然主要在神经元细胞中表达的 ATL1 的融合活性比 ATL2 或 ATL3 弱，但添加神经元特异性因子 M1-spastin 显著增加了 ATL1 介导的脂质体融合。尽管我们观察到从主要表达 ATL2-1（ATL2 的自动抑制同工型）的培养的非神经元细胞中分离的 ER 微粒之间有效的融合，但正如先前报道的那样，ATL2-1 本身不能支持脂质体融合，表明细胞因子使 ATL2-1 能够在体内介导 ER 融合。
