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RalA and RalB differentially regulate development of epithelial tight junctions
Journal article   Open access   Peer reviewed

RalA and RalB differentially regulate development of epithelial tight junctions

C. Clayton Hazelett, David Sheff and Charles Yeaman
Molecular biology of the cell, Vol.22(24), pp.4787-4800
12/15/2011
DOI: 10.1091/mbc.e11-07-0657
PMCID: PMC3237622
PMID: 22013078
url
https://doi.org/10.1091/mbc.e11-07-0657View
Published (Version of record) Open Access

Abstract

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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