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Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta4 cytoplasmic domain

C Murgia1, P Blaikie, N Kim

  • 1Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

The EMBO Journal
|July 22, 1998
PubMed

Insights

The integrin beta4 cytoplasmic domain is essential for stable epithelial adhesion and proper cell division. Its deletion causes severe skin blistering and developmental defects, mimicking junctional epidermolysis bullosa with pyloric atresia.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Dermatology

Background:

  • The integrin alpha6beta4 is a key component of hemidesmosomes, mediating epithelial cell adhesion to the basement membrane.
  • The cytoplasmic tail of beta4 is known to interact with cytoskeletal proteins and signaling molecules like Shc.

Purpose of the Study:

  • To investigate the developmental role of the integrin beta4 cytoplasmic domain.
  • To elucidate the function of beta4 tail-mediated interactions in epithelial integrity and cell proliferation.

Main Methods:

  • Generation of mice with a targeted deletion of the beta4 cytoplasmic domain.
  • Analysis of mutant mice for epidermal integrity, adhesion, and cell proliferation.
  • Assessment of molecular changes in intestinal and skin epithelial cells.

Main Results:

  • Tail-less alpha6beta4 binds laminin 5 but fails to integrate with the cytoskeleton.
  • Mutant mice exhibit severe epidermal detachment at birth, leading to immediate death, resembling PA-JEB.
  • A significant reduction in precursor cell populations and altered cell-cycle regulation (increased p27Kip) were observed in remaining epithelia.

Conclusions:

  • The beta4 cytoplasmic domain is critical for stable adhesion of stratified epithelia to the basement membrane.
  • Beta4 tail interactions are essential for regulating cell-cycle control in both stratified and simple epithelia.
  • This study highlights the dual role of the beta4 tail in adhesion and proliferation, crucial for epithelial development and homeostasis.

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