title: Palmitoylation of plakophilin is required for desmosome assembly.
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 plakophilin-dependent 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.
authors.affiliation: The University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln, NE 68583, USA.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Roberts
authors.affiliation: The University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln, NE 68583, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Johnson
authors.affiliation: Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: McGuinn
authors.affiliation: The University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln, NE 68583, USA.
authors.forename: Jintana
authors.initials: J
authors.lastname: Saowapa
authors.affiliation: The University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln, NE 68583, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Svoboda
authors.affiliation: Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
authors.forename: My G
authors.initials: MG
authors.lastname: Mahoney
authors.affiliation: The University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln, NE 68583, USA Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68198, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Johnson
authors.affiliation: The University of Nebraska Medical Center, College of Dentistry, Department of Oral Biology, Lincoln, NE 68583, USA jwahl@unmc.edu.
authors.forename: James K
authors.initials: JK
authors.lastname: Wahl
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D051180:Desmoplakins / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D006801:Humans; D054878:Lipoylation / Q000502:physiology*; D051191:Plakophilins / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism
chemical_list: D051180:Desmoplakins; D051191:Plakophilins; D051185:gamma Catenin
keywords: Desmosome; Palmitoylation; Plakophilin