Regulation of epithelial apical junctions and barrier function by Gα13
Author(s)
Donato, Rino
Wood, Stephen A
Saunders, Ian
Gundsambuu, Batjargal
Mak, Kai Yan
Abbott, Catherine A
Powell, Barry C
Griffith University Author(s)
Year published
2009
Metadata
Show full item recordAbstract
The epithelial tight junction forms a barrier to paracellular solute movement. In this study we show that the heterotrimeric G-protein Ga13 regulates the epithelial tight junction barrier. We generated MDCKII kidney epithelial cell lines in which the expression of an active Ga13 mutant (Ga13Q226L) could be induced. We demonstrated that Ga13Q226L expression increased paracellular permeability and caused the disruption and redistribution of proteins comprising the tight junction and the adherens junction away from sites of cell contact and the appearance of basal stress fibers. The effects on the junctional proteins and the ...
View more >The epithelial tight junction forms a barrier to paracellular solute movement. In this study we show that the heterotrimeric G-protein Ga13 regulates the epithelial tight junction barrier. We generated MDCKII kidney epithelial cell lines in which the expression of an active Ga13 mutant (Ga13Q226L) could be induced. We demonstrated that Ga13Q226L expression increased paracellular permeability and caused the disruption and redistribution of proteins comprising the tight junction and the adherens junction away from sites of cell contact and the appearance of basal stress fibers. The effects on the junctional proteins and the actin cytoskeleton were abrogated by the Rho kinase inhibitor Y27632 but not by the Src kinase inhibitor PP2. The Ga13 mediated increase in permeability was also Src kinase independent but was partly dependent on Rho kinase signalling. Our data establish a link between Ga13, Rho kinase signaling and epithelial barrier function and not only demonstrate that Ga13 regulates epithelial apical junction properties but that it does so via signaling pathways that are distinct from the closely related protein Ga12.
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View more >The epithelial tight junction forms a barrier to paracellular solute movement. In this study we show that the heterotrimeric G-protein Ga13 regulates the epithelial tight junction barrier. We generated MDCKII kidney epithelial cell lines in which the expression of an active Ga13 mutant (Ga13Q226L) could be induced. We demonstrated that Ga13Q226L expression increased paracellular permeability and caused the disruption and redistribution of proteins comprising the tight junction and the adherens junction away from sites of cell contact and the appearance of basal stress fibers. The effects on the junctional proteins and the actin cytoskeleton were abrogated by the Rho kinase inhibitor Y27632 but not by the Src kinase inhibitor PP2. The Ga13 mediated increase in permeability was also Src kinase independent but was partly dependent on Rho kinase signalling. Our data establish a link between Ga13, Rho kinase signaling and epithelial barrier function and not only demonstrate that Ga13 regulates epithelial apical junction properties but that it does so via signaling pathways that are distinct from the closely related protein Ga12.
View less >
Journal Title
Biochimica et Biophysica Acta - Molecular Cell Research
Volume
1793
Issue
7
Subject
Biochemistry and cell biology
Cellular interactions (incl. adhesion, matrix, cell wall)
Medical microbiology