Palmitoylation of desmoglein 2 is a regulator of assembly dynamics and protein turnover

Brett J. Roberts, Robert A. Svoboda, Andrew M. Overmiller, Joshua D. Lewis, Andrew P. Kowalczyk, My G. Mahoney, Keith R. Johnson, James K. Wahl

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics. In this study, we have focused on the palmitoylation of the desmosomal cadherin desmoglein-2 (Dsg2) and characterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured cells. We identified two cysteine residues in the juxtamembrane (intracellular anchor) domain of Dsg2 that, when mutated, eliminate its palmitoylation. These cysteine residues are conserved in all four desmoglein family members. Although mutant Dsg2 localizes to endogenous desmosomes, there is a significant delay in its incorporation into junctions, and the mutant is also present in a cytoplasmic pool. Triton X-100 solubility assays demonstrate that mutant Dsg2 is more soluble than wild-type protein. Interestingly, trafficking of the mutant Dsg2 to the cell surface was delayed, and a pool of the non-palmitoylated Dsg2 co-localized with lysosomal markers. Taken together, these data suggest that palmitoylation of Dsg2 regulates protein transport to the plasma membrane. Modulation of the palmitoylation status of desmosomal cadherins can affect desmosome dynamics.

Original languageEnglish (US)
Pages (from-to)24857-24865
Number of pages9
JournalJournal of Biological Chemistry
Volume291
Issue number48
DOIs
StatePublished - Nov 25 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Roberts, B. J., Svoboda, R. A., Overmiller, A. M., Lewis, J. D., Kowalczyk, A. P., Mahoney, M. G., Johnson, K. R., & Wahl, J. K. (2016). Palmitoylation of desmoglein 2 is a regulator of assembly dynamics and protein turnover. Journal of Biological Chemistry, 291(48), 24857-24865. https://doi.org/10.1074/jbc.M116.739458