Integrin Dynamics and Matrix Assembly : Tensin-dependent Translocation of a 5 b 1 Integrins Promotes Early Fibronectin Fibrillogenesis
Integrin Dynamics and Matrix Assembly : Tensin-dependent Translocation of a 5 b 1 Integrins Promotes Early Fibronectin Fibrillogenesis
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发表时间：
2000
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通讯作者：
R. Pankov;E. Cukierman;B. Katz;Kazue Matsumoto;D. C. Lin;Shin Lin;Cornelia S. Hahn;Kenneth M. Yamada
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作者：
R. Pankov;E. Cukierman;B. Katz;Kazue Matsumoto;D. C. Lin;Shin Lin;Cornelia S. Hahn;Kenneth M. Yamada
纤连蛋白基质组装是一个多步骤的整合素依赖性过程。为了研究整合素动力学在纤连蛋白原纤维形成中的作用，我们开发了一种抗体追踪技术，用于通过不同的抗体同时追踪两个整合素群体。我们确定了玻连蛋白受体a v B 3保留在病灶接触内，而纤连蛋白受体a 5 B 1从病灶接触移位到细胞外基质（ECM）接触中并沿着接触移位。这种电梯样易位发生相对于在6.5 - 6 - 0.7 m/h的焦点接触，是独立的细胞迁移。它由α 5 B 1整联蛋白的连接诱导，并依赖于与功能性肌动蛋白细胞骨架和玻连蛋白受体连接的相互作用。在细胞铺展过程中，配体占据的α 5 B 1整联蛋白的易位远离焦点接触并沿着肌动蛋白丝束产生ECM接触。张力蛋白是这些ECM接触的主要细胞骨架组分，并且张力蛋白的新型显性负性抑制剂阻断ECM接触形成、整合素易位和纤连蛋白原纤维形成而不影响焦点接触。我们建议，易位5 B 1整合素诱导初始纤连蛋白原纤维通过传输细胞因子产生的张力细胞外纤连蛋白分子。通过多种治疗阻断这种整联蛋白易位防止ECM接触和纤连蛋白原纤维形成的形成。这些研究确定了一个本地化的，定向的，整合素易位机制矩阵组装。
Fibronectin matrix assembly is a multistep, integrin-dependent process. To investigate the role of integrin dynamics in fibronectin fibrillogenesis, we developed an antibody-chasing technique for simultaneous tracking of two integrin populations by different antibodies. We established that whereas the vitronectin receptor a v b 3 remains within focal contacts, the fibronectin receptor a 5 b 1 translocates from focal contacts into and along extracellular matrix (ECM) contacts. This escalator-like translocation occurs relative to the focal contacts at 6.5 6 0.7 m m/h and is independent of cell migration. It is induced by ligation of a 5 b 1 integrins and depends on interactions with a functional actin cytoskeleton and vitronectin receptor ligation. During cell spreading, translocation of ligand-occupied a 5 b 1 integrins away from focal contacts and along bundles of actin filaments generates ECM contacts. Tensin is a primary cytoskeletal component of these ECM contacts, and a novel dominant-negative inhibitor of tensin blocked ECM contact formation, integrin translocation, and fibronectin fibrillogenesis without affecting focal contacts. We propose that translocating a 5 b 1 integrins induce initial fibronectin fibrillogenesis by transmitting cytoskeleton-generated tension to extracellular fibronectin molecules. Blocking this integrin translocation by a variety of treatments prevents the formation of ECM contacts and fibronectin fibrillogenesis. These studies identify a localized, directional, integrin translocation mechanism for matrix assembly.