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-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.
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, AustriaDivision of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Natalia
N
Schiefermeier
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Julia M
JM
Scheffler
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Mariana E G
ME
de Araujo
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Taras
T
Stasyk
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Teodor
T
Yordanov
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, AustriaDivision of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Hannes L
HL
Ebner
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Martin
M
Offterdinger
VIB Center for the Biology of Disease, KU Leuven, 3000 Leuven, Belgium.
Sebastian
S
Munck
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Michael W
MW
Hess
Paul Gerson Unna group "Skin Homeostasis and Ageing", Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Sara A
SA
Wickström
Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Anika
A
Lange
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria Oncotyrol, 6020 Innsbruck, Austria.
Winfried
W
Wunderlich
Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Reinhard
R
Fässler
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria.
David
D
Teis
Division of Cell Biology and Division of Neurobiochemistry/Biooptics, Biocenter, Department of Physiology and Medical Physics, Division of Physiology, Department of Traumatology, Center of Operative Medicine, and Division of Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria lukas.a.huber@i-med.ac.at.
Lukas A
LA
Huber
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D022001:Focal Adhesions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C581820:Arl8B protein, mouse; C101203:IQ motif containing GTPase activating protein 1; C426009:LAMTOR2 protein, mouse; C114559:Lamtor3 protein, mouse; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D020727:ADP-Ribosylation Factors