| First Author | Xu S | Year | 2019 |
| Journal | Biol Open | Volume | 8 |
| Issue | 8 | PubMed ID | 31362952 |
| Mgi Jnum | J:279690 | Mgi Id | MGI:6343170 |
| Doi | 10.1242/bio.041913 | Citation | Xu S, et al. (2019) Discoidin domain receptor 1 deficiency in vascular smooth muscle cells leads to mislocalisation of N-cadherin contacts. Biol Open 8(8):bio041913 |
| abstractText | N-cadherin mediates cell-cell contacts in vascular smooth muscle cells (VSMCs), and regulates VSMC behaviours including migration and proliferation. Discoidin domain receptor 1 (DDR1) is a collagen binding receptor also implicated in these processes. Previous studies have shown that both N-cadherin and DDR1 are upregulated after vascular injury, but it is not known whether there is a relationship between the two molecules. In the current study we found that N-cadherin was mislocalised from cell-cell junctions in the absence of DDR1. This occurred in spite of the fact that there was no significant difference in total cell lysate levels of N-cadherin between DDR1+/+ and DDR1-/- VSMCs. Analysis of lipid raft fractions revealed decreased N-cadherin and associated junctional complex catenins in DDR1-/- compared to DDR1+/+ VSMCs. Treatment with cholesterol oxidase or methyl-beta-cyclodextrin to disrupt lipid rafts removed N-cadherin and DDR1 from the raft fractions. Reciprocal co-immunoprecipitations suggested the association of DDR1 and N-cadherin. Importantly, transfection of DDR1-/- cells with full-length DDR1b rescued the formation of N-cadherin junctions. Together, these data reveal that N-cadherin cell-cell contacts in VSMCs are regulated through interactions with DDR1 and both molecules are located in lipid rafts. |
