Desmosome assembly and disassembly are membrane raft-dependent

Sara N. Stahley, Masataka Saito, Victor Faundez, Michael Koval, Alexa L. Mattheyses, Andrew P. Kowalczyk

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 raftcontaining 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.

Original languageEnglish
Article numbere87809
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - 2014 Jan 30
Externally publishedYes

Fingerprint

Desmoglein 3
desmosomes
Desmosomes
Membranes
Desmosomal Cadherins
Adhesion
Pemphigus
adhesion
Skin
Cholesterol
cadherins
Tissue
skin (animal)
cholesterol
Membrane Microdomains
Adhesives
Microscopic examination
intermediate filaments
Immunoglobulin G
Mechanical Stress

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Stahley, S. N., Saito, M., Faundez, V., Koval, M., Mattheyses, A. L., & Kowalczyk, A. P. (2014). Desmosome assembly and disassembly are membrane raft-dependent. PLoS One, 9(1), [e87809]. https://doi.org/10.1371/journal.pone.0087809

Desmosome assembly and disassembly are membrane raft-dependent. / Stahley, Sara N.; Saito, Masataka; Faundez, Victor; Koval, Michael; Mattheyses, Alexa L.; Kowalczyk, Andrew P.

In: PLoS One, Vol. 9, No. 1, e87809, 30.01.2014.

Research output: Contribution to journalArticle

Stahley, SN, Saito, M, Faundez, V, Koval, M, Mattheyses, AL & Kowalczyk, AP 2014, 'Desmosome assembly and disassembly are membrane raft-dependent', PLoS One, vol. 9, no. 1, e87809. https://doi.org/10.1371/journal.pone.0087809
Stahley SN, Saito M, Faundez V, Koval M, Mattheyses AL, Kowalczyk AP. Desmosome assembly and disassembly are membrane raft-dependent. PLoS One. 2014 Jan 30;9(1). e87809. https://doi.org/10.1371/journal.pone.0087809
Stahley, Sara N. ; Saito, Masataka ; Faundez, Victor ; Koval, Michael ; Mattheyses, Alexa L. ; Kowalczyk, Andrew P. / Desmosome assembly and disassembly are membrane raft-dependent. In: PLoS One. 2014 ; Vol. 9, No. 1.
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