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PLoS One. 2014 Jan 30;9(1):e87809. doi: 10.1371/journal.pone.0087809. eCollection 2014.

Desmosome assembly and disassembly are membrane raft-dependent.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, United States of America ; Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
2
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
3
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, United States of America ; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
4
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, United States of America ; Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, United States of America ; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Abstract

Strong intercellular adhesion is critical for tissues that experience mechanical stress, such as the skin and heart. Desmosomes provide adhesive strength to tissues by anchoring desmosomal cadherins of neighboring cells to the intermediate filament cytoskeleton. Alterations in assembly and disassembly compromise desmosome function and may contribute to human diseases, such as the autoimmune skin blistering disease pemphigus vulgaris (PV). We previously demonstrated that PV auto-antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3) cause loss of adhesion by triggering membrane raft-mediated Dsg3 endocytosis. We hypothesized that raft membrane microdomains play a broader role in desmosome homeostasis by regulating the dynamics of desmosome assembly and disassembly. In human keratinocytes, Dsg3 is raft associated as determined by biochemical and super resolution immunofluorescence microscopy methods. Cholesterol depletion, which disrupts rafts, prevented desmosome assembly and adhesion, thus functionally linking rafts to desmosome formation. Interestingly, Dsg3 did not associate with rafts in cells lacking desmosomal proteins. Additionally, PV IgG-induced desmosome disassembly occurred by redistribution of Dsg3 into raft-containing endocytic membrane domains, resulting in cholesterol-dependent loss of adhesion. These findings demonstrate that membrane rafts are required for desmosome assembly and disassembly dynamics, suggesting therapeutic potential for raft targeting agents in desmosomal diseases such as PV.

PMID:
24498201
PMCID:
PMC3907498
DOI:
10.1371/journal.pone.0087809
[Indexed for MEDLINE]
Free PMC Article

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