Document Type

Article

Publication Date

11-25-2016

Comments

This article has been peer reviewed. This research was originally published in the Journal of Biological Chemistry. Roberts, B. J., Svoboda, R. A., Overmiller, A. M., Lewis, J. D., Kowalczyk, A. P., Mahoney, M. G., Johnson, K.R., & Wahl, J. K.,III. Palmitoylation of desmoglein 2 is a regulator of assembly dynamics and protein turnover. Journal of Biological Chemistry. November 2016; Volume 291, Issue 48: 24857-24865. © the American Society for Biochemistry and Molecular Biology

The published version is available at DOI: 10.1074/jbc.M116.739458.

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.

Available for download on Saturday, November 25, 2017

Share

COinS