Chao Wei-Ting, Kunz Jeannette
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, 1 Baylor Plaza, BCM335, RM T419, Houston, TX 77030, USA.
FEBS Lett. 2009 Apr 17;583(8):1337-43. doi: 10.1016/j.febslet.2009.03.037. Epub 2009 Mar 22.
Cell migration requires the controlled disassembly of focal adhesions, but the underlying mechanisms remain poorly understood. Here, we show that adhesion turnover is mediated through dynamin- and clathrin-dependent endocytosis of activated beta1 integrins. Consistent with this, clathrin and the clathrin adaptors AP-2 and disabled-2 (DAB2) distribute along with dynamin 2 to adhesion sites prior to adhesion disassembly. Moreover, knockdown of either dynamin 2 or both clathrin adaptors blocks beta1 integrin internalization, leading to impaired focal adhesion disassembly and cell migration. Together, these results provide important insight into the mechanisms underlying adhesion disassembly and identify novel components of the disassembly pathway.
细胞迁移需要粘着斑的可控拆解,但其潜在机制仍知之甚少。在此,我们表明粘着更新是通过动力蛋白和网格蛋白依赖的活化β1整合素内吞作用介导的。与此一致的是,在粘着拆解之前,网格蛋白以及网格蛋白衔接蛋白AP-2和失活-2(DAB2)与动力蛋白2一起分布到粘着位点。此外,动力蛋白2或两种网格蛋白衔接蛋白的敲低均会阻断β1整合素的内化,导致粘着斑拆解受损和细胞迁移受阻。总之,这些结果为粘着拆解的潜在机制提供了重要见解,并鉴定出拆解途径的新组分。