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

Elife. 2023 Jul 5:12:RP87037. doi: 10.7554/eLife.87037.

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 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.

Keywords: C. elegans; basement membrane; cell biology; developmental biology; discoidin domain receptor; endocytosis; integrin; tissue connection; type IV collagen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Cell Adhesion / physiology
  • Collagen / metabolism
  • Discoidin Domain Receptor 2* / metabolism
  • Discoidin Domain Receptors / metabolism
  • Female
  • Integrins*
  • Signal Transduction

Substances

  • Discoidin Domain Receptors
  • Integrins
  • Collagen
  • Discoidin Domain Receptor 2