title: Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation.
abstract: The pathways driving desmosome and adherens junction assembly are temporally and spatially coordinated, but how they are functionally coupled is poorly understood. Here we show that the Armadillo protein plakophilin 3 (Pkp3) mediates both desmosome assembly and E-cadherin maturation through Rap1 GTPase, thus functioning in a manner distinct from the closely related plakophilin 2 (Pkp2). Whereas Pkp2 and Pkp3 share the ability to mediate the initial phase of desmoplakin (DP) accumulation at sites of cell-cell contact, they play distinct roles in later steps: Pkp3 is required for assembly of a cytoplasmic population of DP-enriched junction precursors, whereas Pkp2 is required for transfer of the precursors to the membrane. Moreover, Pkp3 forms a complex with Rap1 GTPase, promoting its activation and facilitating desmosome assembly. We show further that Pkp3 deficiency causes disruption of an E-cadherin/Rap1 complex required for adherens junction sealing. These findings reveal Pkp3 as a coordinator of desmosome and adherens junction assembly and maturation through its functional association with Rap1.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
authors.forename: Viktor
authors.initials: V
authors.lastname: Todorovic
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Koetsier
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Godsel
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 R.H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 kgreen@northwestern.edu.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Green
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D051180:Desmoplakins / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D006801:Humans; D051191:Plakophilins / Q000235:genetics* / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000235:genetics*
chemical_list: D015820:Cadherins; D051180:Desmoplakins; C495337:PKP2 protein, human; C495339:PKP3 protein, human; D051191:Plakophilins; D020827:rap1 GTP-Binding Proteins