Department of Biology, Duke University, Durham, United States.
Department of Cell Biology, Duke University Medical Center, Durham, United States.
Elife. 2023 Jul 5;12:RP87037. doi: 10.7554/eLife.87037.
Separate tissues connect through adjoining basement membranes to carry out molecular barrier, exchange, and organ support functions. Cell adhesion at these connections must be robust and balanced to withstand independent tissue movement. Yet, how cells achieve synchronized adhesion to connect tissues is unknown. Here, we have investigated this question using the utse-seam tissue connection that supports the uterus during egg-laying. Through genetics, quantitative fluorescence, and cell-specific molecular disruption, we show that type IV collagen, which fastens the linkage, also activates the collagen receptor discoidin domain receptor-2 (DDR-2) in both the utse and seam. RNAi depletion, genome editing, and photobleaching experiments revealed that DDR-2 signals through LET-60/Ras to coordinately strengthen an integrin adhesion in the utse and seam that stabilizes their connection. These results uncover a synchronizing mechanism for robust adhesion during tissue connection, where collagen both affixes the linkage and signals to both tissues to bolster their adhesion.
分隔组织通过相邻的基膜连接，以执行分子屏障、交换和器官支持功能。这些连接处的细胞黏附必须强大且平衡，以承受独立组织的运动。然而，细胞如何实现同步黏附以连接组织尚不清楚。在这里，我们使用支持产卵时子宫的 utse- seam 组织连接来研究这个问题。通过遗传学、定量荧光和细胞特异性分子破坏，我们表明，连接的固定物 IV 型胶原也在 utse 和 seam 中激活胶原受体 discoidin 结构域受体-2（DDR-2）。RNAi 耗尽、基因组编辑和光漂白实验表明，DDR-2 通过 LET-60/Ras 信号传导，协调增强 utse 和 seam 中的整联蛋白黏附，从而稳定它们的连接。这些结果揭示了组织连接过程中强大黏附的同步机制，其中胶原既固定连接，又向两个组织发出信号以增强它们的黏附。
