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Published on: June 13, 2014
Interaction of integrins alpha 3 beta 1 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion
B E Symington1, Y Takada, W G Carter
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Insights
Integrins alpha 2 beta 1 and alpha 3 beta 1 mediate intercellular adhesion (ICA) in keratinocytes. These integrins interact with each other and with ligands like collagen, suggesting a dual role in cell adhesion.
Area of Science:
- Cell Biology
- Dermatology
- Integrin Biology
Background:
- Integrins alpha 2 beta 1 and alpha 3 beta 1 are found at keratinocyte contact sites.
- These integrins are implicated in mediating intercellular adhesion (ICA).
Purpose of the Study:
- To investigate the role of integrins alpha 2 beta 1 and alpha 3 beta 1 in keratinocyte intercellular adhesion (ICA).
- To explore the potential interaction between integrins alpha 2 beta 1 and alpha 3 beta 1.
Main Methods:
- Utilized intercellular adhesion (ICA) assays with cultured keratinocytes and epidermis.
- Employed assays with purified, monoclonal antibody-immobilized integrins.
- Investigated ligand binding of integrins expressed in CHO fibroblasts.
Main Results:
- An anti-alpha 3 beta 1 antibody (P1B5) induced ICA, mediated by both alpha 2 beta 1 and alpha 3 beta 1.
- Selective binding was observed between alpha 2 beta 1-coated beads and epidermal cells, and between plate-bound alpha 3 beta 1.
- Demonstrated a selective, inhibitable interaction between purified alpha 2 beta 1 and alpha 3 beta 1 integrins.
- CHO fibroblasts expressing alpha 2 beta 1 showed binding to collagen and alpha 3 beta 1, inhibited by an anti-alpha 2 beta 1 antibody (P1H5).
Conclusions:
- Integrins alpha 2 beta 1 and alpha 3 beta 1 can interact with each other.
- This interaction suggests a mechanism for mediating intercellular adhesion (ICA) in vivo.
- Integrin alpha 3 beta 1 mediates keratinocyte adhesion to epiligrin and also participates in ICA through interaction with alpha 2 beta 1.
Abstract:
The colocalization of integrins alpha 2 beta 1 and alpha 3 beta 1 at intercellular contact sites of keratinocytes in culture and in epidermis suggests that these integrins may mediate intercellular adhesion (ICA). P1B5, an anti-alpha 3 beta 1 mAb previously reported to inhibit keratinocyte adhesion to epiligrin, was also found to induce ICA. Evidence that P1B5-induced ICA was mediated by alpha 2 beta 1 and alpha 3 beta 1 was obtained using both ICA assays and assays with purified, mAb-immobilized integrins. Selective binding of alpha 2 beta 1-coated beads to epidermal cells or plate-bound alpha 3 beta 1 was observed. This binding was inhibited by mAbs to integrin alpha 3, alpha 2, or beta 1 subunits and could be stimulated by P1B5. We also demonstrate a selective and inhibitable interaction between affinity-purified integrins alpha 2 beta 1 and alpha 3 beta 1. Finally, we show that expression of alpha 2 beta 1 by CHO fibroblasts results in the acquisition of collagen and alpha 3 beta 1 binding. Binding to both of these ligands is inhibited by P1H5, an anti-alpha 2 beta 1 specific mAb. Results of these in vitro experiments suggest that integrins alpha 2 beta 1 and alpha 3 beta 1 can interact and may do so to mediate ICA in vivo. Thus, alpha 3 beta 1 mediates keratinocyte adhesion to epiligrin and plays a second role in ICA via alpha 2 beta 1.
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