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

The study explored the effects of specific mutations in the β1 integrin cytoplasmic tail on embryonic development and epidermal function. Mice with tyrosine-to-alanine mutations (β1 Y783A and β1 Y795A) experienced embryonic lethality similar to β1-null mice, but these mutations resulted in milder skin and hair follicle issues when expressed in the epidermis. The research concluded that talin and kindlin regulate β1 integrin adhesion differently in keratinocytes compared to embryonic cells, with the NPxY motifs contributing independently to β1 function. Single mutations in keratinocytes caused subtle defects, while double mutations led to a β1-null phenotype. The study highlighted that β1 integrin adhesion could occur without direct talin or kindlin binding, although it was delayed and functionally compromised, underscoring the critical role of β1 integrins in embryonic development.