The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA
The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA
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DOI：
10.1242/jcs.046219
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发表时间：
2009-05-15
影响因子：
4
通讯作者：
Vogel, Wolfgang F.
中科院分区：
文献类型：
--
作者：
Huang, Yun;Arora, Pamela;Vogel, Wolfgang F.
细胞在粘附基质上的扩散和迁移是由收缩力和突出力的平衡调节的。非肌肉肌球蛋白IIA是一种普遍表达的收缩蛋白和酶，参与调节细胞在各种刺激下的扩散和定向迁移。在这里，我们发现盘状蛋白结构域受体1 (DDR1)，一种被I型胶原激活的酪氨酸激酶受体，在配体刺激下与非肌肉肌球蛋白IIA重链（NMHC-IIA）结合。NMHC-IIA的共免疫沉淀也表明了与全长DDR1的关联，但与缺乏激酶结构域的截断的DDR1 -异构体没有关联。DDR1对NMHC-IIA在胶原细胞上组装成细丝很重要。DDR1的表达抑制细胞在胶原蛋白上的扩散，但促进细胞迁移。相比之下，blebbistatin阻断非肌肉肌球蛋白II活性可促进细胞扩散，但抑制胶原蛋白迁移。我们认为肌球蛋白和DDR1通过调节与胶原蛋白的粘附接触来影响细胞的扩散和迁移。
The spreading and migration of cells on adhesive substrates is regulated by the counterbalance of contractile and protrusive forces. Non-muscle myosin IIA, an ubiquitously expressed contractile protein and enzyme, is implicated in the regulation of cell spreading and directional migration in response to various stimuli. Here we show that discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor activated by type I collagen, associates with the non-muscle myosin IIA heavy chain (NMHC-IIA) upon ligand stimulation. An association was also indicated by coimmunoprecipitation of NMHC-IIA with full-length DDR1, but not with the truncated DDR1d-isoform lacking the kinase domain. DDR1 was important for assembly of NMHC-IIA into filaments on cells plated on collagen. DDR1 expression inhibited cell spreading over collagen but promoted cell migration. By contrast, blockade of non-muscle myosin II activity by blebbistatin enhanced cell spreading but inhibited migration over collagen. We propose that myosin and DDR1 impact cell spreading and migration by regulating adhesive contacts with collagen.