TY - JOUR
T1 - Integrins traffic rapidly via circular dorsal ruffles and macropinocytosis during stimulated cell migration
AU - Gu, Zhizhan
AU - Noss, Erika H.
AU - Hsu, Victor W.
AU - Brenner, Michael B.
PY - 2011/4/4
Y1 - 2011/4/4
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201007003
DO - 10.1083/jcb.201007003
M3 - Article
C2 - 21464228
AN - SCOPUS:79955493637
SN - 0021-9525
VL - 193
SP - 61
EP - 70
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -