Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction
Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction
复制标题
盘状结构域受体1介导肌球蛋白依赖的胶原收缩
DOI：
10.1016/j.celrep.2017.01.061
复制
发表时间：
2017-02-14
期刊：
影响因子：
8.8
通讯作者：
McCulloch, Christopher A.
中科院分区：
文献类型：
--
作者：
Coelho, Nuno M.;Arora, Pamma D.;McCulloch, Christopher A.
Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced > 30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen. Tractional remodeling of collagen was dependent on DDR1 clustering, activation, and interaction of the DDR1 C-terminal kinase domain with NMIIA filaments. Collagen remodeling by traction forces, DDR1 tyrosine phosphorylation, and myosin light chain phosphorylation were increased on stiff versus soft substrates. Thus, DDR1 clustering, activation, and interaction with NMIIA filaments enhance the collagen tractional remodeling that is important for collagen compaction in fibrosis.
