Laminin polymerization induces a receptor-cytoskeleton network.
Laminin polymerization induces a receptor-cytoskeleton network.
复制标题
层粘连蛋白聚合诱导受体细胞骨架网络。
DOI：
10.1083/jcb.145.3.619
复制
发表时间：
1999-05-03
影响因子：
7.8
通讯作者：
Yurchenco, P D
中科院分区：
文献类型：
--
作者：
Colognato, H;Winkelmann, D A;Yurchenco, P D
层粘连蛋白从单体态向聚合态的转变被认为是基底膜发育的关键步骤，就骨骼肌而言，层粘连蛋白的突变可导致伴有基底膜缺陷的严重肌营养不良症。我们评估了层粘连蛋白聚合物和受体的相互作用，以确定层粘连蛋白在细胞表面组装的要求，并研究了这种转变可能介导的细胞反应。我们发现，在肌肉细胞表面，层粘连蛋白优先聚合，同时与包括肌营养不良聚糖和 α7β1 整合素在内的受体结合。这些受体相互作用是通过层粘连蛋白 COOH 末端结构域介导的，这些结构域在空间和功能上与 NH2 末端聚合物结合位点不同。这种受体促进的自组装驱动层粘连蛋白重排成细胞相关的多边形网络，这一过程也需要肌动蛋白重组和酪氨酸磷酸化。结果，肌营养不良聚糖和整合素重新分布成互惠网络，皮质细胞骨架成分纽蛋白和肌营养不良蛋白也是如此。细胞骨架和受体重组依赖于层粘连蛋白聚合，并且不能单独响应受体占据（非聚合层粘连蛋白）。层粘连蛋白在细胞表面的优先聚合以及由此产生的皮质结构的诱导是一个协作过程，需要层粘连蛋白-受体连接、受体促进的自组装、肌动蛋白重组和信号传导事件。
The transition of laminin from a monomeric to a polymerized state is thought to be a crucial step in the development of basement membranes and in the case of skeletal muscle, mutations in laminin can result in severe muscular dystrophies with basement membrane defects. We have evaluated laminin polymer and receptor interactions to determine the requirements for laminin assembly on a cell surface and investigated what cellular responses might be mediated by this transition. We found that on muscle cell surfaces, laminins preferentially polymerize while bound to receptors that included dystroglycan and α7β1 integrin. These receptor interactions are mediated through laminin COOH-terminal domains that are spatially and functionally distinct from NH2-terminal polymer binding sites. This receptor-facilitated self-assembly drives rearrangement of laminin into a cell-associated polygonal network, a process that also requires actin reorganization and tyrosine phosphorylation. As a result, dystroglycan and integrin redistribute into a reciprocal network as do cortical cytoskeleton components vinculin and dystrophin. Cytoskeletal and receptor reorganization is dependent on laminin polymerization and fails in response to receptor occupancy alone (nonpolymerizing laminin). Preferential polymerization of laminin on cell surfaces, and the resulting induction of cortical architecture, is a cooperative process requiring laminin– receptor ligation, receptor-facilitated self-assembly, actin reorganization, and signaling events.