Abstract
Discoidin domain receptor 1 (DDR1) is a widely expressed receptor tyrosine kinase (RTK) which regulates cell differentiation, proliferation and migration and remodeling of the extracellular matrix. Collagen(s) are the only known ligand for DDR1. We have previously reported that collagen stimulation leads to oligomerization of the full length receptor. In this study we investigated the effect of oligomerization of the DDR1 extracellular domain (ECD) pre and post ligand binding. Solid phase binding assays showed that oligomers of recombinant DDR1-Fc bound more strongly to collagen compared to dimeric DDR1-Fc alone. In addition, DDR1-Fc itself could oligomerize upon in-vitro binding to collagen when examined using atomic force microscopy. Inhibition of dynamin mediated receptor endocytosis could prevent ligand induced endocytosis of DDR1b-YFP in live cells. However inhibition of receptor endocytosis did not affect DDR1 oligomerization. In summary our results demonstrate that DDR1 ECD plays a crucial role in receptor oligomerization which mediates high-affinity interactions with its ligand.