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Published on: June 13, 2014
A cell surface desmosome-associated component: identification of tissue-specific cell adhesion molecule
Summary
Autoantibodies targeting a 140-kDa glycoprotein (GP) in pemphigus vulgaris disrupt cell adhesion. This study identifies the 140-kDa GP as a cell adhesion molecule involved in desmosome function.
Area of Science:
- Dermatology
- Cell Biology
- Immunology
Background:
- Pemphigus vulgaris is a blistering skin disease caused by autoantibodies.
- These autoantibodies target desmosomal proteins, leading to epidermal acantholysis.
- Desmosomes are crucial for cell-cell adhesion in stratified squamous epithelia.
Purpose of the Study:
- To characterize the 140-kDa glycoprotein (GP) recognized by pemphigus vulgaris autoantibodies.
- To investigate the localization and function of this 140-kDa GP within desmosomes.
- To explore the role of the 140-kDa GP in cell adhesion and tissue specificity.
Main Methods:
- Immunofluorescence microscopy on bovine tongue epidermis and cultured mouse keratinocytes.
- Affinity purification of antibodies against the 140-kDa GP.
- Double immunofluorescence with desmoplakin antiserum.
- Immunogold electron microscopy for ultrastructural localization.
- Functional assays assessing cell-cell contact disruption.
Main Results:
- Autoantibodies from pemphigus vulgaris patients recognize a 140-kDa glycoprotein (GP) in epidermal desmosomes.
- Antibodies to the 140-kDa GP produced a punctate intercellular staining pattern in epidermis and recognized desmosomes in keratinocytes.
- Ultrastructural localization revealed the 140-kDa antigen on the cell surface and within desmosomes, distinct from desmoplakin.
- Antibodies to the 140-kDa GP disrupted cell-cell contacts in cultured keratinocytes.
Conclusions:
- The 140-kDa GP is a cell adhesion molecule (CAM) involved in keratinocyte adhesion.
- The 140-kDa GP plays a role in desmosome structure and function.
- Findings suggest heterogeneity in desmosomes and tissue-specific recognition of the 140-kDa GP.
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