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Abstract:
Cell migration is mediated by the dynamic remodeling
of focal adhesions (FAs). Recently, an important
role of endosomal signaling in regulation of
cell migration was recognized. Here, we show an essential
function for late endosomes carrying the p14–MP1
(LAMTOR2/3) complex in FA dynamics. p14–MP1-positive
endosomes move to the cell periphery along microtubules
(MTs) in a kinesin1- and Arl8b-dependent manner. There
they specifically target FAs to regulate FA turnover, which is required for cell migration. Using genetically modified
fibroblasts from p14-deficient mice and Arl8b-depleted
cells, we demonstrate that MT plus end–directed traffic of
p14–MP1-positive endosomes triggered IQGAP1 disassociation
from FAs. The release of IQGAP was required
for FA dynamics. Taken together, our results suggest that
late endosomes contribute to the regulation of cell migration
by transporting the p14–MP1 scaffold complex to the
vicinity of FAs.
