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Journal Article

beta 1 Integrins with Individually Disrupted Cytoplasmic NPxY Motifs Are Embryonic Lethal but Partially Active in the Epidermis

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons78767

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

http://pubman.mpdl.mpg.de/cone/persons/resource/persons77774

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

http://pubman.mpdl.mpg.de/cone/persons/resource/persons77945

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

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Citation

Meves, A., Stremmel, C., Böttcher, R. T., & Fässler, R. (2013). beta 1 Integrins with Individually Disrupted Cytoplasmic NPxY Motifs Are Embryonic Lethal but Partially Active in the Epidermis. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133(12), 2722-2731. doi:10.1038/jid.2013.232.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-C2DC-B
Abstract
beta 1 Integrin adhesion is believed to require binding of talins and kindlins to the membrane proximal and distal NPxY motifs of the beta 1 cytoplasmic tail, respectively. To test this hypothesis, we substituted the membrane proximal and distal tyrosines (Y) of the beta 1 tail with alanine (A) residues (beta 1 Y783A; beta 1 Y795A) in the germline of mice. We report that beta 1 Y783A or beta 1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to beta 1 null-like peri-implantation lethality. Expression of beta 1 Y783A or beta 1 Y795A in the epidermis, however, resulted in skin blister and hair follicle phenotypes that were considerably milder than those observed with beta 1 integrin gene deletion or a beta 1 double Y-to-A substitution (beta 1 YY783/795AA). In culture, defects in adhesion, spreading, and migration were more severe with the beta 1 Y783A than with the beta 1 Y795A substitution despite markedly reduced b1 Y795A integrin surface levels owing to diminished protein stability. We conclude that regulation of beta 1 integrin adhesion through talins and kindlins may differ substantially between stably adherent keratinocytes and cells of the developing embryo, and that beta 1 cytoplasmic NPxY motifs contribute individually and independent of each other to beta 1 function in keratinocytes.