Mellentine Samuel Q, Ramsey Anna S, Li Jie, Brown Hunter N, Tootle Tina L
Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
bioRxiv. 2023 Jun 26:2023.06.23.546291. doi: 10.1101/2023.06.23.546291.
A key regulator of collective cell migration is prostaglandin (PG) signaling. However, it remains largely unclear whether PGs act within the migratory cells or their microenvironment to promote migration. Here we use border cell migration as a model to uncover the cell-specific roles of two PGs in collective migration. Prior work shows PG signaling is required for on-time migration and cluster cohesion. We find that the PGE synthase cPGES is required in the substrate, while the PGF synthase Akr1B is required in the border cells for on-time migration. Akr1B acts in both the border cells and their substrate to regulate cluster cohesion. One means by which Akr1B regulates border cell migration is by promoting integrin-based adhesions. Additionally, Akr1B limits myosin activity, and thereby cellular stiffness, in the border cells, whereas cPGES limits myosin activity in both the border cells and their substrate. Together these data reveal that two PGs, PGE and PGF, produced in different locations, play key roles in promoting border cell migration. These PGs likely have similar migratory versus microenvironment roles in other collective cell migrations.
前列腺素（PG）信号传导是集体细胞迁移的关键调节因子。然而，PG是在迁移细胞内还是在其微环境中发挥作用以促进迁移，目前仍不清楚。在这里，我们以边界细胞迁移为模型，来揭示两种PG在集体迁移中细胞特异性的作用。先前的研究表明，PG信号传导对于准时迁移和细胞簇凝聚是必需的。我们发现，底物中需要PGE合酶cPGES，而边界细胞中需要PGF合酶Akr1B来实现准时迁移。Akr1B在边界细胞及其底物中均发挥作用，以调节细胞簇凝聚。Akr1B调节边界细胞迁移的一种方式是促进基于整合素的黏附。此外，Akr1B限制边界细胞中的肌球蛋白活性，从而限制细胞硬度，而cPGES则限制边界细胞及其底物中的肌球蛋白活性。这些数据共同表明，在不同位置产生的两种PG，即PGE和PGF，在促进边界细胞迁移中起关键作用。这些PG在其他集体细胞迁移中可能具有类似的迁移与微环境作用。
