Rab13 regulates PKA signaling during tight junction assembly |
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Authors: | Köhler Katja Louvard Daniel Zahraoui Ahmed |
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Institution: | Laboratory of Morphogenesis and Cell Signaling, Centre National de la Recherche Scientifique, UMR144 Institut Curie, 26 rue d'Ulm, 75248, Paris, Cedex 05, France. |
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Abstract: | The GTPase Rab13 regulates the assembly of functional epithelial tight junctions (TJs) through a yet unknown mechanism. Here, we show that expression of the GTP-bound form of Rab13 inhibits PKA-dependent phosphorylation and TJ recruitment of the vasodilator-stimulated phosphoprotein, an actin remodelling protein. We demonstrate that Rab13GTP directly binds to PKA and inhibits its activity. Interestingly, activation of PKA abrogates the inhibitory effect of Rab13 on the recruitment of vasodilator-stimulated phosphoprotein, ZO-1, and claudin1 to cell-cell junctions. Rab13 is, therefore, the first GTPase that controls PKA activity and provides an unexpected link between PKA signaling and the dynamics of TJ assembly. |
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Keywords: | Rab GTPase phosphorylation VASP cell–cell junctions epithelial cells |
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