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

Abstract

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 C. 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.

DNA methylation characteristics associated with chemotherapy resistance in epithelial ovarian cancer

“…The two main receptors for type IV collagen are integrin and the discoidin domain receptor (DDR). DDR2, one of the two DDR genes, plays a role in promoting attachment at the tissue linkage site in utse and seam cells [ 34 ]. Several studies have demonstrated the critical role of DDR2 in breast cancer progression and metastasis, both in tumor cells and stromal cells [ 35 ].…”