title: Palmitoylation of Desmoglein 2 Is a Regulator of Assembly Dynamics and Protein Turnover.
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.
authors.affiliation: From the Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska 68583.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Roberts
authors.affiliation: From the Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska 68583.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Svoboda
authors.affiliation: the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Overmiller
authors.affiliation: the Departments of Cell Biology and Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: the Departments of Cell Biology and Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Kowalczyk
authors.affiliation: the Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and.
authors.forename: My G
authors.initials: MG
authors.lastname: Mahoney
authors.affiliation: From the Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska 68583.|the Eppley Institute for Research in Cancer and Allied Diseases, Omaha, Nebraska 68198.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Johnson
authors.affiliation: From the Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska 68583, jwahl@unmc.edu.
authors.forename: James K
authors.initials: JK
authors.lastname: Wahl
mesh_terms: D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism*; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054878:Lipoylation / Q000502:physiology*; D020125:Mutation, Missense; D021381:Protein Transport / Q000502:physiology
chemical_list: C495314:DSG2 protein, human; D051301:Desmoglein 2
keywords: cadherin; desmoglein; desmosome; lipid raft; protein palmitoylation