| First Author | Meves A | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 12 | Pages | 2722-2731 |
| PubMed ID | 23702582 | Mgi Jnum | J:203018 |
| Mgi Id | MGI:5523765 | Doi | 10.1038/jid.2013.232 |
| Citation | Meves A, et al. (2013) beta1 Integrins with Individually Disrupted Cytoplasmic NPxY Motifs Are Embryonic Lethal but Partially Active in the Epidermis. J Invest Dermatol 133(12):2722-31 |
| abstractText | beta1 Integrin adhesion is believed to require binding of talins and kindlins to the membrane proximal and distal NPxY motifs of the beta1 cytoplasmic tail, respectively. To test this hypothesis, we substituted the membrane proximal and distal tyrosines (Y) of the beta1 tail with alanine (A) residues (beta1 Y783A; beta1 Y795A) in the germline of mice. We report that beta1 Y783A or beta1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to beta1 null-like peri-implantation lethality. Expression of beta1 Y783A or beta1 Y795A in the epidermis, however, resulted in skin blister and hair follicle phenotypes that were considerably milder than those observed with beta1 integrin gene deletion or a beta1 double Y-to-A substitution (beta1 YY783/795AA). In culture, defects in adhesion, spreading, and migration were more severe with the beta1 Y783A than with the beta1 Y795A substitution despite markedly reduced beta1 Y795A integrin surface levels owing to diminished protein stability. We conclude that regulation of beta1 integrin adhesion through talins and kindlins may differ substantially between stably adherent keratinocytes and cells of the developing embryo, and that beta1 cytoplasmic NPxY motifs contribute individually and independent of each other to beta1 function in keratinocytes. |
