The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration
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-po...
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| Veröffentlicht in: | The Journal of cell biology 2014-05, Vol.205 (4), p.525-540 |
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| creator | Schiefermeier, Natalia Scheffler, Julia M de Araujo, Mariana E G Stasyk, Taras Yordanov, Teodor Ebner, Hannes L Offterdinger, Martin Munck, Sebastian Hess, Michael W Wickström, Sara A Lange, Anika Wunderlich, Winfried Fässler, Reinhard Teis, David Huber, Lukas A |
| description | 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. |
| doi_str_mv | 10.1083/jcb.201310043 |
| format | Article |
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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. 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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. 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| subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism ADP-Ribosylation Factors - metabolism Animals Cell adhesion & migration Cell Line Cell Movement - physiology Endosomes - metabolism Fibroblasts - cytology Focal Adhesions - metabolism Genetics HeLa Cells Humans Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data NIH 3T3 Cells Proteins - genetics Proteins - metabolism ras GTPase-Activating Proteins - genetics ras GTPase-Activating Proteins - metabolism Rodents Signal Transduction - physiology |
| title | The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration |
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