| First Author | Klapproth S | Year | 2019 |
| Journal | J Cell Biol | Volume | 218 |
| Issue | 10 | Pages | 3436-3454 |
| PubMed ID | 31537712 | Mgi Jnum | J:280278 |
| Mgi Id | MGI:6364636 | Doi | 10.1083/jcb.201903109 |
| Citation | Klapproth S, et al. (2019) A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability. J Cell Biol 218(10):3436-3454 |
| abstractText | 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. |
