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A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability.

Authors :
Klapproth S
Bromberger T
Türk C
Krüger M
Moser M
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.)

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