Universität zu Köln

Klapproth, Sarah, Bromberger, Thomas, Tuerk, Clara, Krueger, Marcus ORCID: 0000-0003-2008-4582 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:	Creators Email ORCID ORCID Put Code Klapproth, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Bromberger, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Tuerk, Clara UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Moser, Markus UNSPECIFIED orcid.org/0000-0001-8825-5566 UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL ADHESION; TYROSINE PHOSPHORYLATION; PTP-PEST; INTEGRIN ACTIVATION; STRUCTURAL BASIS; ADAPTER PROTEIN; ILK-COMPLEX; PAXILLIN; LEUPAXIN; KINDLIN Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13272