Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells.
Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells.
复制标题
DOI：
10.1083/jcb.200904054
复制
发表时间：
2009-11-30
期刊：
影响因子：
--
通讯作者：
Gundersen GG
中科院分区：
文献类型：
--
作者：
Ezratty EJ;Bertaux C;Marcantonio EE;Gundersen GG
一个新的机制，局部粘连拆卸涉及微管刺激内吞的整合素在局部粘连。粘着斑解体是由微管（MT）通过一个未知的机制，涉及发动蛋白。为了测试是否可能涉及内吞作用，我们干扰网格蛋白或其衔接子常染色体隐性遗传性高脂血症（ARH）和Dab 2（残疾人-2）的功能，发现这两种治疗方法都能防止MT诱导的局灶性粘连解体。表面标记实验表明，整合素是内吞在细胞外基质，网格蛋白，ARH和Dab 2依赖的方式进入Rab 5内体之前。网格蛋白共定位与一个子集的局灶性粘连的ARH和Dab 2依赖的方式。直接成像显示网格蛋白在MT刺激的拆卸过程中迅速积聚在粘着斑上，并在其拆卸后与整合素一起离开粘着斑。在迁移细胞中，网格蛋白或Dab 2和ARH的耗竭抑制了粘着斑的解体，并降低了迁移率。这些结果表明，粘着斑解体通过涉及MT、网格蛋白和特定网格蛋白衔接子的靶向机制发生，并且粘着斑的整合素的直接内吞介导其在迁移细胞中的解体。
A new mechanism for focal adhesion disassembly is described involving microtubule-stimulated endocytosis of integrins at focal adhesions. Focal adhesion disassembly is regulated by microtubules (MTs) through an unknown mechanism that involves dynamin. To test whether endocytosis may be involved, we interfered with the function of clathrin or its adaptors autosomal recessive hypercholesteremia (ARH) and Dab2 (Disabled-2) and found that both treatments prevented MT-induced focal adhesion disassembly. Surface labeling experiments showed that integrin was endocytosed in an extracellular matrix–, clathrin-, and ARH- and Dab2-dependent manner before entering Rab5 endosomes. Clathrin colocalized with a subset of focal adhesions in an ARH- and Dab2-dependent fashion. Direct imaging showed that clathrin rapidly accumulated on focal adhesions during MT-stimulated disassembly and departed from focal adhesions with integrin upon their disassembly. In migrating cells, depletion of clathrin or Dab2 and ARH inhibited focal adhesion disassembly and decreased the rate of migration. These results show that focal adhesion disassembly occurs through a targeted mechanism involving MTs, clathrin, and specific clathrin adaptors and that direct endocytosis of integrins from focal adhesions mediates their disassembly in migrating cells.
登录
查看更多内容
DOI：
10.1083/jcb.153.7.1427
发表时间：
2001-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Laukaitis CM;Webb DJ;Donais K;Horwitz AF
通讯作者：
Horwitz AF
影响因子：
11.8
作者：
Nishimura, Takashi;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
影响因子：
4.8
作者：
Hocevar, BA;Prunier, C;Howe, PH
通讯作者：
Howe, PH
影响因子：
4.8
作者：
Benmerah, A;Poupon, V;Dautry-Varsat, A
通讯作者：
Dautry-Varsat, A
影响因子：
4.3
作者：
Echarri, Asier;Del Pozo, Miguel A.
通讯作者：
Del Pozo, Miguel A.