Integrins traffic rapidly via circular dorsal ruffles and macropinocytosis during stimulated cell migration
Open Access
- 4 April 2011
- journal article
- other
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 193 (1), 61-70
- https://doi.org/10.1083/jcb.201007003
Abstract
During cell migration, integrins are redistributed from focal adhesions undergoing disassembly at the cell’s trailing edges to new focal adhesions assembling at leading edges. The initial step of integrin redistribution is thought to require clathrin-mediated endocytosis. However, whether clathrin-mediated endocytosis functions in different contexts, such as basal versus stimulated migration, has not been determined. In this paper, we examine the spatial and temporal redistribution of integrins from focal adhesions upon stimulation by growth factors. Four-dimensional confocal live-cell imaging along with functional analysis reveals that surface integrins do not undergo significant endocytosis at ventral focal adhesions upon cell stimulation with the platelet-derived growth factor. Rather, they abruptly redistribute to dorsal circular ruffles, where they are internalized through macropinocytosis. The internalized integrins then transit through recycling endosomal compartments to repopulate newly formed focal adhesions on the ventral surface. These findings explain why integrins have long been observed to redistribute through both surface-based and internal routes and identify a new function for macropinocytosis during growth factor–induced cell migration.Keywords
This publication has 39 references indexed in Scilit:
- Integrins: masters and slaves of endocytic transportNature Reviews Molecular Cell Biology, 2009
- Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cellsThe Journal of cell biology, 2009
- Focal adhesion disassembly requires clathrin‐dependent endocytosis of integrinsFEBS Letters, 2009
- On the shape of migrating cells — a `front-to-back' modelJournal of Cell Science, 2008
- Coexpression of two mesenchymal cadherins, cadherin 11 and N‐cadherin, on murine fibroblast‐like synoviocytesArthritis & Rheumatism, 2008
- CtBP3/BARS drives membrane fission in dynamin-independent transport pathwaysNature, 2005
- Foot and mouth: podosomes, invadopodia and circular dorsal rufflesNature Reviews Molecular Cell Biology, 2004
- Marching at the front and dragging behindThe Journal of cell biology, 2001
- Comparison of rapid changes in surface morphology and coated pit formation of PC12 cells in response to nerve growth factor, epidermal growth factor, and dibutyryl cyclic AMP.The Journal of cell biology, 1984
- Rapid induction of morphological changes in human carcinoma cells A-431 by epidermal growth factors.The Journal of cell biology, 1979