Abstract
Annexin-2 is required for the apical transport in epithelial cells. In this study, we investigated the involvement of annexin-2 in cAMP-induced aquaporin-2 (AQP2) translocation to the apical membrane in renal cells. We found that the cAMP-elevating agent forskolin increased annexin-2 abundance in the plasma membrane enriched fraction with a parallel decrease in the soluble fraction. Interestingly, forskolin stimulation resulted in annexin-2 enrichment in lipid rafts, suggesting that hormonal stimulation might be responsible for a new configuration of membrane interacting proteins involved in the fusion of AQP2 vesicles to the apical plasma membrane. To investigate the functional involvement of annexin-2 in AQP2 exocytosis, the fusion process between purified AQP2 membrane vesicles and plasma membranes was reconstructed in vitro and monitored by a fluorescence assay. An N-terminal peptide that comprises 14 residues of annexin-2 and that includes the binding site for the calcium binding protein p11 strongly inhibited the fusion process. Preincubation of cells with this annexin-2 peptide also failed to increase the osmotic water permeability in the presence of forskolin in intact cells. Altogether, these data demonstrate that annexin-2 is required for cAMP-induced AQP2 exocytosis in renal cells.
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Acknowledgement
This work was supported by grants from Telethon (proposal no. GGP04202 to G. Valenti), from PRIN (Research Program of National Interest) to G. Valenti, from Centro di Eccellenza di Genomica in campo Biomedico ed Agrario (CEGBA), and from the Regional Project 2007 to G. Valenti.
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Tamma, G., Procino, G., Mola, M.G. et al. Functional involvement of Annexin-2 in cAMP induced AQP2 trafficking. Pflugers Arch - Eur J Physiol 456, 729–736 (2008). https://doi.org/10.1007/s00424-008-0453-1
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DOI: https://doi.org/10.1007/s00424-008-0453-1