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

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.

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 Creators:
Meves, Alexander1, Author
Stremmel, Christopher2, Author              
Böttcher, Ralph T.2, Author              
Fässler, Reinhard2, Author              
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: INTEGRIN ACTIVATION; TALIN; PHOSPHORYLATION; ADHESION; SKIN; EXPRESSION; KINDLIN-3; TYROSINES; PROTEINS; BINDING
 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.

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Language(s): eng - English
 Dates: 2013-12
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000327015400013
DOI: 10.1038/jid.2013.232
 Degree: -

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Title: JOURNAL OF INVESTIGATIVE DERMATOLOGY
Source Genre: Journal
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Publ. Info: 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 133 (12) Sequence Number: - Start / End Page: 2722 - 2731 Identifier: ISSN: 0022-202X