Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells
| Autor: | Eugene E. Marcantonio, Gregg G. Gundersen, Ellen J. Ezratty, Claire Bertaux |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Integrins
Endosome Integrin Nerve Tissue Proteins Biology Endocytosis Microtubules Clathrin Article Focal adhesion Extracellular matrix Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Cell polarity Animals Research Articles Adaptor Proteins Signal Transducing 030304 developmental biology Dynamin Focal Adhesions 0303 health sciences Cell Polarity Membrane Proteins Cell Biology Cell biology Adaptor Proteins Vesicular Transport NIH 3T3 Cells biology.protein RNA Interference Apoptosis Regulatory Proteins 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200904054 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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