Interaction of DDR1 with Collagen Type IV
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Date
2021-05
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The Ohio State University
Abstract
Collagen type IV (Col IV) is a network forming collagen that is the major component of the basement membrane underlying endothelial and epithelial cells. Discoidin Domain Receptor 1 (DDR1) is a receptor tyrosine kinase present on these cells that binds to and gets activated by Col IV (Agarwal et al. 2019). In this study, we investigated how DDR1 impacts the Col IV α1α1α2 network both in-vivo and in-vitro. Analysis of cerebral artery cross sections in electron microscopy images revealed that mice lacking DDR1 had reduced basement membrane thickness, as compared to their wild-type littermates. In-vitro binding of recombinant DDR1 ectodomain (DDR1-Fc) to purified Col IV was verified using solid-state binding assay and single molecule Atomic Force Microscopy (AFM). AFM images of DDR1-Fc binding to Col IV also revealed that DDR1 modulates its network formation. This insight reveals a new functional role of DDR1 in regulating basement membranes.