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The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration
Natalia Schiefermeier1, Julia M Scheffler2, Mariana E G de Araujo2
1Division 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.
Late endosomes carrying the p14-MP1 complex regulate cell migration by moving to focal adhesions. This movement controls focal adhesion turnover through IQGAP1 release, essential for cell motility.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell migration is crucial for development and disease.
- Focal adhesions (FAs) are key regulators of cell migration.
- Endosomal signaling is increasingly recognized for its role in cell migration.
Purpose of the Study:
- To investigate the role of late endosomes and the p14-MP1 complex in focal adhesion dynamics.
- To elucidate the mechanism by which endosomes regulate FA turnover and cell migration.
Main Methods:
- Utilized genetically modified fibroblasts from p14-deficient mice.
- Employed Arl8b-depleted cells to study endosome trafficking.
- Investigated the movement of p14-MP1-positive endosomes along microtubules (MTs).
- Analyzed the disassociation of IQGAP1 from FAs.
Main Results:
- p14-MP1-positive endosomes traffic to the cell periphery via kinesin-1 and Arl8b.
- These endosomes specifically target FAs to regulate FA turnover.
- MT plus end-directed endosome traffic triggers IQGAP1 release from FAs.
- IQGAP1 release is essential for FA dynamics and cell migration.
Conclusions:
- Late endosomes carrying the p14-MP1 complex are essential for regulating FA dynamics.
- Endosome-mediated transport of p14-MP1 to FAs controls FA turnover and cell migration.
- This pathway highlights a novel mechanism linking endosomal signaling to cell motility.