Jang Eunhong, Jun Youngsoo
Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Integrated Institute of Biomedical Research, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Biochem Soc Trans. 2025 Jun 30;53(3):699-707. doi: 10.1042/BST20253043.
Atlastins (ATLs) are integral dynamin-like GTPases that are critical for the formation and maintenance of the endoplasmic reticulum (ER) network, one of the most complex and essential organelles in eukaryotic cells. The ER, which is composed of interconnected tubules and sheets, serves vital functions, including calcium storage, protein and lipid synthesis, and inter-organelle communication. Homotypic membrane fusion, mediated by ATLs, ensures the tubular structure of the ER by generating and stabilizing three-way junctions. Humans express three ATL paralogs, called ATL1, ATL2, and ATL3, which have distinct expression patterns and regulatory mechanisms. Mutations in these proteins are linked to hereditary sensory neuropathies and hereditary spastic paraplegia, highlighting their critical importance in cellular and neuronal health. Here, we review recent studies providing insights into how ATLs are regulated by their N- and C-terminal extensions, as well as how extrinsic factors potentially regulate the activities of ATLs to establish and maintain the normal ER structure.
Atlastins（ATLs）是一类与发动蛋白相似的整合型GTP酶，对于内质网（ER）网络的形成和维持至关重要，内质网是真核细胞中最复杂且必不可少的细胞器之一。内质网由相互连接的小管和片层组成，具有重要功能，包括钙储存、蛋白质和脂质合成以及细胞器间通讯。由ATLs介导的同型膜融合通过产生和稳定三向连接来确保内质网的管状结构。人类表达三种ATL旁系同源物，分别称为ATL1、ATL2和ATL3，它们具有不同的表达模式和调控机制。这些蛋白质的突变与遗传性感觉神经病和遗传性痉挛性截瘫有关，突显了它们在细胞和神经元健康中的关键重要性。在此，我们综述了最近的研究，这些研究深入探讨了ATLs如何受其N端和C端延伸的调控，以及外在因素如何潜在地调控ATLs的活性以建立和维持正常的内质网结构。
