Reciprocal discoidin domain receptor signaling strengthens integrin adhesion to connect adjacent tissues

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 Caenorhabditis elegans 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.

Automated summary

Separate tissues are connected through adjoining basement membranes to fulfill their barrier, exchange, and support functions. The robust and balanced cell adhesion at these connections is essential for withstanding tissue movement. However, the mechanism by which cells achieve synchronized adhesion to connect tissues remains unclear. This study reveals that type IV collagen both fastens the linkage and activates the collagen receptor DDR-2 in the utse and seam tissues, coordinating the strengthening of integrin adhesion through the LET-60/Ras signaling pathway.