Palmitoylation of plakophilin is required for desmosome assembly

Brett J. Roberts, Kristen E. Johnson, Kathleen P. McGuinn, Jintana Saowapa, Robert A. Svoboda, My G. Mahoney, Keith R Johnson, James K Wahl

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Desmosomes are prominent adhesive junctions found in various epithelial tissues. The cytoplasmic domains of desmosomal cadherins interact with a host of desmosomal plaque proteins, including plakophilins, plakoglobin and desmoplakin, which, in turn, recruit the intermediate filament cytoskeleton to sites of cell-cell contact. Although the individual components of the desmosome are known, mechanisms regulating the assembly of this junction are poorly understood. Protein palmitoylation is a posttranslational lipid modification that plays an important role in protein trafficking and function. Here, we demonstrate that multiple desmosomal components are palmitoylated in vivo. Pharmacologic inhibition of palmitoylation disrupts desmosome assembly at cell-cell borders. We mapped the site of plakophilin palmitoylation to a conserved cysteine residue present in the armadillo repeat domain. Mutation of this single cysteine residue prevents palmitoylation, disrupts plakophilin incorporation into the desmosomal plaque and prevents plakophilindependent desmosome assembly. Finally, plakophilin mutants unable to become palmitoylated act in a dominant-negative manner to disrupt proper localization of endogenous desmosome components and decrease desmosomal adhesion. Taken together, these data demonstrate that palmitoylation of desmosomal components is important for desmosome assembly and adhesion.

Original languageEnglish (US)
Pages (from-to)3782-3793
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number17
DOIs
StatePublished - Jan 1 2014

Fingerprint

Plakophilins
Lipoylation
Desmosomes
Cysteine
Desmosomal Cadherins
Desmoplakins
gamma Catenin
Armadillos
Intermediate Filaments
Protein Transport
Post Translational Protein Processing
Cytoskeleton
Adhesives
Proteins
Epithelium
Lipids
Mutation

Keywords

  • Desmosome
  • Palmitoylation
  • Plakophilin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Roberts, B. J., Johnson, K. E., McGuinn, K. P., Saowapa, J., Svoboda, R. A., Mahoney, M. G., ... Wahl, J. K. (2014). Palmitoylation of plakophilin is required for desmosome assembly. Journal of Cell Science, 127(17), 3782-3793. https://doi.org/10.1242/jcs.149849

Palmitoylation of plakophilin is required for desmosome assembly. / Roberts, Brett J.; Johnson, Kristen E.; McGuinn, Kathleen P.; Saowapa, Jintana; Svoboda, Robert A.; Mahoney, My G.; Johnson, Keith R; Wahl, James K.

In: Journal of Cell Science, Vol. 127, No. 17, 01.01.2014, p. 3782-3793.

Research output: Contribution to journalArticle

Roberts, BJ, Johnson, KE, McGuinn, KP, Saowapa, J, Svoboda, RA, Mahoney, MG, Johnson, KR & Wahl, JK 2014, 'Palmitoylation of plakophilin is required for desmosome assembly', Journal of Cell Science, vol. 127, no. 17, pp. 3782-3793. https://doi.org/10.1242/jcs.149849
Roberts BJ, Johnson KE, McGuinn KP, Saowapa J, Svoboda RA, Mahoney MG et al. Palmitoylation of plakophilin is required for desmosome assembly. Journal of Cell Science. 2014 Jan 1;127(17):3782-3793. https://doi.org/10.1242/jcs.149849
Roberts, Brett J. ; Johnson, Kristen E. ; McGuinn, Kathleen P. ; Saowapa, Jintana ; Svoboda, Robert A. ; Mahoney, My G. ; Johnson, Keith R ; Wahl, James K. / Palmitoylation of plakophilin is required for desmosome assembly. In: Journal of Cell Science. 2014 ; Vol. 127, No. 17. pp. 3782-3793.
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