Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Kindlin-1 controls Wnt and TGF-beta availability to regulate cutaneous stem cell proliferation

MPG-Autoren
/persons/resource/persons78576

Rognoni,  Emanuel
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78879

Widmaier,  Moritz
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons104438

Jakobson,  Madis
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78591

Ruppert,  Raphael
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78818

Ussar,  Siegfried
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons130609

Katsougkri,  Despoina
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77774

Böttcher,  Ralph T.
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77945

Fässler,  Reinhard
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

Externe Ressourcen
Volltexte (frei zugänglich)

emss-57003.pdf
(Postprint), 4MB

Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Rognoni, E., Widmaier, M., Jakobson, M., Ruppert, R., Ussar, S., Katsougkri, D., et al. (2014). Kindlin-1 controls Wnt and TGF-beta availability to regulate cutaneous stem cell proliferation. Nature Medicine, 20(4), 350-359. doi:10.1038/nm.3490.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0019-8B93-8
Zusammenfassung
Kindlin-1 is an integrin tail binding protein that controls integrin activation. Mutations in the FERMT-1 gene, which encodes for Kindlin-1, lead to Kindler syndrome in man, which is characterized by skin blistering, premature skin aging and skin cancer of unknown etiology. Here we show that loss of Kindlin-1 in mouse keratinocytes recapitulates Kindler syndrome and also produces enlarged and hyperactive stem cell compartments, which lead to hyperthickened epidermis, ectopic hair follicle development and increased skin tumor susceptibility. Mechanistically, Kindlin-1 controls keratinocyte adhesion through beta 1-class integrins and proliferation and differentiation of cutaneous epithelial stem cells by promoting alpha(nu)beta(6) integrin-mediated transforming growth factor-beta (TGF-beta) activation and inhibiting Wnt-beta-catenin signaling through integrin-independent regulation of Wnt ligand expression. Our findings assign Kindlin-1 the previously unknown and essential task of controlling cutaneous epithelial stem cell homeostasis by balancing TGF-beta-mediated growth-inhibitory signals and Wnt-beta-catenin-mediated growth-promoting signals.