β1 integrins with individually disrupted cytoplasmic NPxY motifs are embryonic lethal but partially active in the epidermis

Alexander Meves, Christopher Stremmel, Ralph T. Böttcher, Reinhard Fässler

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

β1 Integrin adhesion is believed to require binding of talins and kindlins to the membrane proximal and distal NPxY motifs of the β1 cytoplasmic tail, respectively. To test this hypothesis, we substituted the membrane proximal and distal tyrosines (Y) of the β1 tail with alanine (A) residues (β1 Y783A; β1 Y795A) in the germline of mice. We report that β1 Y783A or β1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to β1 null-like peri-implantation lethality. Expression of β1 Y783A or β1 Y795A in the epidermis, however, resulted in skin blister and hair follicle phenotypes that were considerably milder than those observed with β1 integrin gene deletion or a β1 double Y-to-A substitution (β1 YY783/795AA). In culture, defects in adhesion, spreading, and migration were more severe with the β1 Y783A than with the β1 Y795A substitution despite markedly reduced β1 Y795A integrin surface levels owing to diminished protein stability. We conclude that regulation of β1 integrin adhesion through talins and kindlins may differ substantially between stably adherent keratinocytes and cells of the developing embryo, and that β1 cytoplasmic NPxY motifs contribute individually and independent of each other to β1 function in keratinocytes.

Original languageEnglish (US)
Pages (from-to)2722-2731
Number of pages10
JournalJournal of Investigative Dermatology
Volume133
Issue number12
DOIs
StatePublished - Jan 1 2013

Fingerprint

Talin
Epidermis
Integrins
Substitution reactions
Adhesion
Keratinocytes
Tail
Membranes
Hair Follicle
Protein Stability
Gene Deletion
Blister
Alanine
Tyrosine
Skin
Embryonic Structures
Genes
Phenotype
Defects
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

β1 integrins with individually disrupted cytoplasmic NPxY motifs are embryonic lethal but partially active in the epidermis. / Meves, Alexander; Stremmel, Christopher; Böttcher, Ralph T.; Fässler, Reinhard.

In: Journal of Investigative Dermatology, Vol. 133, No. 12, 01.01.2013, p. 2722-2731.

Research output: Contribution to journalArticle

Meves, Alexander ; Stremmel, Christopher ; Böttcher, Ralph T. ; Fässler, Reinhard. / β1 integrins with individually disrupted cytoplasmic NPxY motifs are embryonic lethal but partially active in the epidermis. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 12. pp. 2722-2731.
@article{e3c1f731ca024d9d9b4ace91de78d70a,
title = "β1 integrins with individually disrupted cytoplasmic NPxY motifs are embryonic lethal but partially active in the epidermis",
abstract = "β1 Integrin adhesion is believed to require binding of talins and kindlins to the membrane proximal and distal NPxY motifs of the β1 cytoplasmic tail, respectively. To test this hypothesis, we substituted the membrane proximal and distal tyrosines (Y) of the β1 tail with alanine (A) residues (β1 Y783A; β1 Y795A) in the germline of mice. We report that β1 Y783A or β1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to β1 null-like peri-implantation lethality. Expression of β1 Y783A or β1 Y795A in the epidermis, however, resulted in skin blister and hair follicle phenotypes that were considerably milder than those observed with β1 integrin gene deletion or a β1 double Y-to-A substitution (β1 YY783/795AA). In culture, defects in adhesion, spreading, and migration were more severe with the β1 Y783A than with the β1 Y795A substitution despite markedly reduced β1 Y795A integrin surface levels owing to diminished protein stability. We conclude that regulation of β1 integrin adhesion through talins and kindlins may differ substantially between stably adherent keratinocytes and cells of the developing embryo, and that β1 cytoplasmic NPxY motifs contribute individually and independent of each other to β1 function in keratinocytes.",
author = "Alexander Meves and Christopher Stremmel and B{\"o}ttcher, {Ralph T.} and Reinhard F{\"a}ssler",
year = "2013",
month = "1",
day = "1",
doi = "10.1038/jid.2013.232",
language = "English (US)",
volume = "133",
pages = "2722--2731",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - β1 integrins with individually disrupted cytoplasmic NPxY motifs are embryonic lethal but partially active in the epidermis

AU - Meves, Alexander

AU - Stremmel, Christopher

AU - Böttcher, Ralph T.

AU - Fässler, Reinhard

PY - 2013/1/1

Y1 - 2013/1/1

N2 - β1 Integrin adhesion is believed to require binding of talins and kindlins to the membrane proximal and distal NPxY motifs of the β1 cytoplasmic tail, respectively. To test this hypothesis, we substituted the membrane proximal and distal tyrosines (Y) of the β1 tail with alanine (A) residues (β1 Y783A; β1 Y795A) in the germline of mice. We report that β1 Y783A or β1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to β1 null-like peri-implantation lethality. Expression of β1 Y783A or β1 Y795A in the epidermis, however, resulted in skin blister and hair follicle phenotypes that were considerably milder than those observed with β1 integrin gene deletion or a β1 double Y-to-A substitution (β1 YY783/795AA). In culture, defects in adhesion, spreading, and migration were more severe with the β1 Y783A than with the β1 Y795A substitution despite markedly reduced β1 Y795A integrin surface levels owing to diminished protein stability. We conclude that regulation of β1 integrin adhesion through talins and kindlins may differ substantially between stably adherent keratinocytes and cells of the developing embryo, and that β1 cytoplasmic NPxY motifs contribute individually and independent of each other to β1 function in keratinocytes.

AB - β1 Integrin adhesion is believed to require binding of talins and kindlins to the membrane proximal and distal NPxY motifs of the β1 cytoplasmic tail, respectively. To test this hypothesis, we substituted the membrane proximal and distal tyrosines (Y) of the β1 tail with alanine (A) residues (β1 Y783A; β1 Y795A) in the germline of mice. We report that β1 Y783A or β1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to β1 null-like peri-implantation lethality. Expression of β1 Y783A or β1 Y795A in the epidermis, however, resulted in skin blister and hair follicle phenotypes that were considerably milder than those observed with β1 integrin gene deletion or a β1 double Y-to-A substitution (β1 YY783/795AA). In culture, defects in adhesion, spreading, and migration were more severe with the β1 Y783A than with the β1 Y795A substitution despite markedly reduced β1 Y795A integrin surface levels owing to diminished protein stability. We conclude that regulation of β1 integrin adhesion through talins and kindlins may differ substantially between stably adherent keratinocytes and cells of the developing embryo, and that β1 cytoplasmic NPxY motifs contribute individually and independent of each other to β1 function in keratinocytes.

UR - http://www.scopus.com/inward/record.url?scp=84887826720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887826720&partnerID=8YFLogxK

U2 - 10.1038/jid.2013.232

DO - 10.1038/jid.2013.232

M3 - Article

C2 - 23702582

AN - SCOPUS:84887826720

VL - 133

SP - 2722

EP - 2731

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 12

ER -