The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China.
The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Nat Cell Biol. 2023 Aug;25(8):1173-1184. doi: 10.1038/s41556-023-01188-8. Epub 2023 Jul 24.
The migrasome is an organelle of migrating cells with diverse physiological functions. How migrasome formation is initiated is unknown. We found that sphingomyelin is enriched in migrasomes and identified sphingomyelin synthase 2 (SMS2) as an essential protein for migrasome biogenesis. SMS2 assembles into immobile foci that adhere on the basal membrane at the leading edge. When cells migrate away, the SMS2 foci 'move' out of cells and into retraction fibres, where they become migrasome formation sites and eventually grow into migrasomes. Mechanistically, SMS2 foci seed migrasomes by converting ceramide to sphingomyelin, which is essential for migrasome formation. Furthermore, CerS5, which is required for the synthesis of long-chain ceramide, and CERT, which transports ceramide from the endoplasmic reticulum to Golgi, are both required for migrasome formation. Our data reveal the essential role of ceramide and sphingomyelin in migrasome formation and suggest that SMS2 forms basal membrane-surface-connecting structures that pre-determine where migrasomes will grow.
迁移小体是一种具有多种生理功能的迁移细胞的细胞器。迁移小体如何形成尚不清楚。我们发现，神经鞘磷脂在迁移小体中富集，并鉴定出神经鞘磷脂合酶 2（SMS2）是迁移小体生物发生的必需蛋白。SMS2 组装成固定焦点，附着在前沿的基底膜上。当细胞迁移时，SMS2 焦点“移出”细胞并进入收缩纤维，在那里它们成为迁移小体形成的部位，并最终生长成迁移小体。从机制上讲，SMS2 焦点通过将神经酰胺转化为神经鞘磷脂来启动迁移小体的形成，这对于迁移小体的形成是必不可少的。此外，合成长链神经酰胺所需的 CerS5 和将神经酰胺从内质网运输到高尔基体的 CERT，对于迁移小体的形成都是必需的。我们的数据揭示了神经酰胺和神经鞘磷脂在迁移小体形成中的重要作用，并表明 SMS2 形成了基底膜-表面连接结构，预先确定了迁移小体将在哪里生长。
