Distinct recycling of active and inactive β1 integrins.
Distinct recycling of active and inactive β1 integrins.
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DOI：
10.1111/j.1600-0854.2012.01327.x
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Ivaska J
中科院分区：
文献类型：
--
作者：
Arjonen A;Alanko J;Veltel S;Ivaska J
整合素运输在细胞运动和细胞质分裂中起着重要作用。整合素通过不断的胞内/胞外穿梭来促进细胞粘附的动态调节。整合素对细胞外基质成分的活性受这些受体在活性和非活性构象之间转换的能力的调节。几种细胞信号通路在不同条件下对整合素交通的调节已经被描述。然而，整合素活性构象与它们的内吞命运之间的相互关系仍然不完全清楚。在这里，我们研究了癌细胞中活性和非活性β1整合素的内吞运输。这两种构象都以网格蛋白和动力蛋白依赖的方式内吞。活性β1整合素的净内吞率更高，而无活性β1整合素的内吞作用通过arf6和早期内体抗原1阳性室以Rab 4a和actin依赖的方式快速循环回质膜而被抵消。由于这些不同的运输路线，两个受体池显示不同的亚细胞定位。在稳态下，失活的β1整合素主要在质膜上，而活性受体主要在细胞内。这些数据为整合素的内吞运输提供了新的见解，并暗示了在调节整合素活性和运输的途径之间以前未被认识到的串扰的可能性。
Integrin trafficking plays an important role in cellular motility and cytokinesis. Integrins undergo constant endo/exocytic shuttling to facilitate the dynamic regulation of cell adhesion. Integrin activity toward the components of the extracellular matrix is regulated by the ability of these receptors to switch between active and inactive conformations. Several cellular signalling pathways have been described in the regulation of integrin traffic under different conditions. However, the interrelationship between integrin activity conformations and their endocytic fate have remained incompletely understood. Here, we have investigated the endocytic trafficking of active and inactive β1 integrins in cancer cells. Both conformers are endocytosed in a clathrin- and dynamin-dependent manner. The net endocytosis rate of the active β1 integrins is higher, whereas endocytosis of the inactive β1 integrin is counteracted by rapid recycling back to the plasma membrane via an ARF 6- and early endosome antigen 1-positive compartment in an Rab 4a- and actin-dependent manner. Owing to these distinct trafficking routes, the two receptor pools display divergent subcellular localization. At steady state, the inactive β1 integrin is mainly on the plasma membrane, whereas the active receptor is predominantly intracellular. These data provide new insights into the endocytic traffic of integrins and imply the possibility of a previously unappreciated crosstalk between pathways regulating integrin activity and traffic.
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