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A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability.
- Source :
-
The Journal of cell biology [J Cell Biol] 2019 Oct 07; Vol. 218 (10), pp. 3436-3454. Date of Electronic Publication: 2019 Sep 19. - Publication Year :
- 2019
-
Abstract
- Binding of kindlins to integrins is required for integrin activation, stable ligand binding, and subsequent intracellular signaling. How hematopoietic kindlin-3 contributes to the assembly and stability of the adhesion complex is not known. Here we report that kindlin-3 recruits leupaxin into podosomes and thereby regulates paxillin phosphorylation and podosome turnover. We demonstrate that the activity of the protein tyrosine phosphatase PTP-PEST, which controls paxillin phosphorylation, requires leupaxin. In contrast, despite sharing the same binding mode with leupaxin, paxillin recruitment into podosomes is kindlin-3 independent. Instead, we found paxillin together with talin and vinculin in initial adhesion patches of kindlin-3-null cells. Surprisingly, despite its presence in these early adhesion patches, podosomes can form in the absence of paxillin or any paxillin member. In conclusion, our findings show that kindlin-3 not only activates and clusters integrins into podosomes but also regulates their lifetime by recruiting leupaxin, which controls PTP-PEST activity and thereby paxillin phosphorylation and downstream signaling.<br /> (© 2019 Klapproth et al.)
- Subjects :
- Animals
Cell Adhesion
Cells, Cultured
Chromatography, Liquid
Cytoskeletal Proteins deficiency
Cytoskeletal Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
RAW 264.7 Cells
Tandem Mass Spectrometry
Cell Adhesion Molecules metabolism
Cytoskeletal Proteins metabolism
Paxillin metabolism
Podosomes metabolism
Signal Transduction
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 218
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 31537712
- Full Text :
- https://doi.org/10.1083/jcb.201903109