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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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Autores principales: Todorovic´, Viktor, Koetsier, Jennifer L., Godsel, Lisa M., Green, Kathleen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230782/
https://www.ncbi.nlm.nih.gov/pubmed/25208567
http://dx.doi.org/10.1091/mbc.E14-05-0968
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author Todorovic´, Viktor
Koetsier, Jennifer L.
Godsel, Lisa M.
Green, Kathleen J.
author_facet Todorovic´, Viktor
Koetsier, Jennifer L.
Godsel, Lisa M.
Green, Kathleen J.
author_sort Todorovic´, Viktor
collection PubMed
description 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.
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spelling pubmed-42307822015-01-30 Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation Todorovic´, Viktor Koetsier, Jennifer L. Godsel, Lisa M. Green, Kathleen J. Mol Biol Cell Articles 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. The American Society for Cell Biology 2014-11-15 /pmc/articles/PMC4230782/ /pubmed/25208567 http://dx.doi.org/10.1091/mbc.E14-05-0968 Text en © 2014 Todorovic´ et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Todorovic´, Viktor
Koetsier, Jennifer L.
Godsel, Lisa M.
Green, Kathleen J.
Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation
title Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation
title_full Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation
title_fullStr Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation
title_full_unstemmed Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation
title_short Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation
title_sort plakophilin 3 mediates rap1-dependent desmosome assembly and adherens junction maturation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230782/
https://www.ncbi.nlm.nih.gov/pubmed/25208567
http://dx.doi.org/10.1091/mbc.E14-05-0968
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