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RalA and RalB differentially regulate development of epithelial tight junctions

Tight junctions (TJs) are structures indispensable to epithelial cells and are responsible for regulation of paracellular diffusion and maintenance of cellular polarity. Although many interactions between TJ constituents have been identified, questions remain concerning how specific functions of TJs...

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Detalles Bibliográficos
Autores principales: Hazelett, C. Clayton, Sheff, David, Yeaman, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237622/
https://www.ncbi.nlm.nih.gov/pubmed/22013078
http://dx.doi.org/10.1091/mbc.E11-07-0657
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author Hazelett, C. Clayton
Sheff, David
Yeaman, Charles
author_facet Hazelett, C. Clayton
Sheff, David
Yeaman, Charles
author_sort Hazelett, C. Clayton
collection PubMed
description Tight junctions (TJs) are structures indispensable to epithelial cells and are responsible for regulation of paracellular diffusion and maintenance of cellular polarity. Although many interactions between TJ constituents have been identified, questions remain concerning how specific functions of TJs are established and regulated. Here we investigated the roles of Ral GTPases and their common effector exocyst complex in the formation of nascent TJs. Unexpectedly, RNA interference–mediated suppression of RalA or RalB caused opposing changes in TJ development. RalA reduction increased paracellular permeability and decreased incorporation of components into TJs, whereas RalB reduction decreased paracellular permeability and increased incorporation of components into TJs. Activities of both Ral GTPases were mediated through the exocyst. Finally, we show that TJ-mediated separation of apical–basal membrane domains is established prior to equilibration of barrier function and that it is unaffected by Ral knockdown or specific composition of TJs.
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spelling pubmed-32376222012-03-01 RalA and RalB differentially regulate development of epithelial tight junctions Hazelett, C. Clayton Sheff, David Yeaman, Charles Mol Biol Cell Articles Tight junctions (TJs) are structures indispensable to epithelial cells and are responsible for regulation of paracellular diffusion and maintenance of cellular polarity. Although many interactions between TJ constituents have been identified, questions remain concerning how specific functions of TJs are established and regulated. Here we investigated the roles of Ral GTPases and their common effector exocyst complex in the formation of nascent TJs. Unexpectedly, RNA interference–mediated suppression of RalA or RalB caused opposing changes in TJ development. RalA reduction increased paracellular permeability and decreased incorporation of components into TJs, whereas RalB reduction decreased paracellular permeability and increased incorporation of components into TJs. Activities of both Ral GTPases were mediated through the exocyst. Finally, we show that TJ-mediated separation of apical–basal membrane domains is established prior to equilibration of barrier function and that it is unaffected by Ral knockdown or specific composition of TJs. The American Society for Cell Biology 2011-12-15 /pmc/articles/PMC3237622/ /pubmed/22013078 http://dx.doi.org/10.1091/mbc.E11-07-0657 Text en © 2011 Hazelett 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 of Cell Biology.
spellingShingle Articles
Hazelett, C. Clayton
Sheff, David
Yeaman, Charles
RalA and RalB differentially regulate development of epithelial tight junctions
title RalA and RalB differentially regulate development of epithelial tight junctions
title_full RalA and RalB differentially regulate development of epithelial tight junctions
title_fullStr RalA and RalB differentially regulate development of epithelial tight junctions
title_full_unstemmed RalA and RalB differentially regulate development of epithelial tight junctions
title_short RalA and RalB differentially regulate development of epithelial tight junctions
title_sort rala and ralb differentially regulate development of epithelial tight junctions
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237622/
https://www.ncbi.nlm.nih.gov/pubmed/22013078
http://dx.doi.org/10.1091/mbc.E11-07-0657
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