Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation

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 GTP...

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Bibliographic Details
Published in:Molecular biology of the cell 2014-11, Vol.25 (23), p.3749-3764
Main Authors: Todorovic, Viktor, Koetsier, Jennifer L, Godsel, Lisa M, Green, Kathleen J
Format: Article
Language:English
Subjects:
Adherens Junctions - genetics
Adherens Junctions - metabolism
Cadherins - genetics
Cadherins - metabolism
Cell Adhesion - genetics
Cell Line
Desmoplakins - metabolism
Desmosomes - metabolism
Humans
Plakophilins - genetics
Plakophilins - metabolism
rap1 GTP-Binding Proteins - genetics
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E14-05-0968