Klapproth, Sarah, Bromberger, Thomas, Tuerk, Clara, Krueger, Marcus and Moser, Markus ORCID: 0000-0001-8825-5566 (2019). A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability. J. Cell Biol., 218 (10). S. 3436 - 3455. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Klapproth, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bromberger, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuerk, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moser, MarkusUNSPECIFIEDorcid.org/0000-0001-8825-5566UNSPECIFIED
URN: urn:nbn:de:hbz:38-132721
DOI: 10.1083/jcb.201903109
Journal or Publication Title: J. Cell Biol.
Volume: 218
Number: 10
Page Range: S. 3436 - 3455
Date: 2019
Publisher: ROCKEFELLER UNIV PRESS
Place of Publication: NEW YORK
ISSN: 1540-8140
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FOCAL ADHESION; TYROSINE PHOSPHORYLATION; PTP-PEST; INTEGRIN ACTIVATION; STRUCTURAL BASIS; ADAPTER PROTEIN; ILK-COMPLEX; PAXILLIN; LEUPAXIN; KINDLINMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13272

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