Rab13 regulates PKA signaling during tight junction assembly.
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.
Köhler
Katja
K
Laboratory of Morphogenesis and Cell Signaling, Centre National de la Recherche Scientifique, UMR144 Institut Curie, 26 rue d'Ulm, 75248, Paris, Cedex 05, France.
Louvard
Daniel
D
Zahraoui
Ahmed
A
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D062445:Claudin-1; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D062445:Claudin-1; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D017868:Cyclic AMP-Dependent Protein Kinases; D020691:rab GTP-Binding Proteins