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Novel function for beta 1 integrins in keratinocyte cell-cell interactions
H Larjava1, J Peltonen, S K Akiyama
1Membrane Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
The Journal of Cell Biology
|March 1, 1990
Summary
Beta 1 integrins are crucial for maintaining cell-cell adhesion and organizing microfilaments in human epidermal keratinocytes. Blocking beta 1 integrins disrupts these functions without affecting cell-substrate adhesion.
Area of Science:
- Cell Biology
- Dermatology
- Integrin Biology
Background:
- Integrins are cell surface receptors mediating cell-extracellular matrix and cell-cell adhesion.
- Beta 1 integrins are a key component of various integrin heterodimers, playing diverse roles in cell adhesion and signaling.
- Keratinocytes, the main cell type in the epidermis, rely on cell-cell and cell-substrate adhesion for tissue integrity.
Purpose of the Study:
- To investigate the expression, localization, and function of beta 1 integrins in cultured human epidermal keratinocytes.
- To determine the specific roles of beta 1 integrins in keratinocyte cell-cell and cell-substrate adhesion.
- To elucidate the involvement of beta 1 integrins in the organization of intracellular structures like F-actin.
Main Methods:
- Utilized polyclonal and monoclonal antibodies against beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits.
- Examined integrin expression and localization using immunofluorescence.
- Assessed the functional role of beta 1 integrins by treating keratinocyte cultures with specific antibodies and observing effects on cell-cell adhesion and F-actin organization.
- Investigated the influence of calcium concentration on antibody-mediated effects.
Main Results:
- Beta 1, alpha 2, and alpha 3 integrin subunits were localized at keratinocyte cell-cell contacts, suggesting a role in cell-cell adhesion.
- The alpha 5 subunit (fibronectin receptor) was diffusely distributed, consistent with fibronectin's absence at cell-cell sites.
- Monoclonal antibody targeting beta 1 integrins dissociated keratinocyte colonies, inhibiting cell-cell adhesion without affecting cell-substrate adhesion.
- Antibody treatment disrupted F-actin filament organization and beta 1 integrin localization, even at high calcium concentrations that prevented antibody-mediated dissociation.
Conclusions:
- Beta 1 integrins play a significant role in maintaining cell-cell contacts between keratinocytes.
- Beta 1 integrins are involved in the organization of intracellular microfilaments in epithelial cells.
- Integrins, specifically beta 1, can function in both cell-cell and cell-substrate adhesion in epithelial cells, highlighting their versatile roles.