2026-08-29 理化学研究所,順天堂大学
ゴルジ体膜の脂質二重層の再編成によるリソソーム酵素輸送とオートファジーの制御
＜関連情報＞
- https://www.riken.jp/press/2026/20260829_1/index.html
- https://www.science.org/doi/10.1126/sciadv.aec4519
リソソーム酵素の選別とオートファジーは、GGA1誘導性TGN脂質スクランブリングによって制御される Sorting of lysosomal enzyme and autophagy are regulated by the GGA1-induced TGN lipid scrambling
Kohta Takahashi, Nario Tomishige, Mitsuhiro Abe, Gašper Šolinc, […] , and Toshihide Kobayashi
Science Advances Published:28 Aug 2026
DOI:https://doi.org/10.1126/sciadv.aec4519
Abstract
The physiological role of lipid asymmetry in intracellular membranes remains poorly understood. Here, we show that sphingomyelin (SM), typically confined to the lumen of the trans-Golgi network (TGN), is exposed on its cytoplasmic surface by the action of the Golgi-associated protein, Golgi-associated gamma-adaptin ear–containing adenosine 5′-diphosphate–ribosylation factor–binding protein 1 (GGA1). This exposure is driven by the GGA1 GAT domain, which induces lipid scrambling in a manner dependent on membrane curvature and cholesterol. SM exposure coincides with the exit of mannose 6-phosphate receptors from the TGN, a process essential for lysosomal enzyme trafficking. Furthermore, SM is transferred to autophagic membranes, where it facilitates autophagosome-lysosome fusion. These findings reveal a previously unrecognized role for lipid remodeling in membrane trafficking and autophagy.
