Istituto di Biofisica     
Valenti G., Procino G., Liebenhoff U., Frigeri A., Benedetti P. A., Ahnert-Hilger G., Nürnberg B., Svelto M., Rosenthal W. A Heterotrimeric G Protein of the Gi Family Is Required for cAMP-triggered Trafficking of Aquaporin 2 in Kidney Epithelial Cells. In: Journal of Biological Chemistry, vol. 273 (35) pp. 22627 - 22634. American Society for Biochemistry and Molecular Biology, 1998.
Vasopressin is the key regulator of water homeostasis in vertebrates. Central to its antidiuretic action in mammals is the redistribution of the water channel aquaporin 2 (AQP2) from intracellular vesicles to the apical membrane of kidney epithelial cells, an event initiated by an increase in cAMP and activation of protein kinase A. The subsequent steps of the signaling cascade are not known. To identify proteins involved in the AQP2 shuttle we exploited a recently developed cell line (CD8) derived from the rabbit cortical collecting duct and stably transfected with rat AQP2 cDNA. Treatment of CD8 cells with pertussis toxin (PTX) inhibited both the vasopressin-induced increase in water permeability and the redistribution of AQP2 from an intracellular compartment to the apical membrane. ADP-ribosylation studies revealed the presence of at least two major PTX substrates. Correspondingly, two alpha subunits of PTX-sensitive G proteins, Galpha i2 and Galpha i3, were identified by Western blotting. Introduction of a synthetic peptide corresponding to the C terminus of the Gi3 alpha subunit into permeabilized CD8 cells efficiently inhibited the cAMP-induced AQP2 translocation; a peptide corresponding to the alpha subunits of Gi1/2 was much less potent. Thus a member of the Gi family, most likely Gi3, is involved in the cAMP-triggered targeting of AQP2-bearing vesicles to the apical membrane of kidney epithelial cells.
URL: http://www.jbc.org/cgi/content/abstract/273/35/22627

Icona documento 1) Download Document PDF

Icona documento Open access Icona documento Restricted Icona documento Private


Per ulteriori informazioni, contattare: Librarian http://puma.isti.cnr.it

Valid HTML 4.0 Transitional