HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/F1308    most recent 00197.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Blount, M. A. Articles by Sands, J. M. Search for Related Content PubMed PubMed Citation Articles by Blount, M. A. Articles by Sands, J. M.

Forskolin stimulates phosphorylation and membrane accumulation of UT-A3

Renal Division, Emory University School of Medicine, Atlanta, Georgia

Submitted 24 April 2007 ; accepted in final form 2 August 2007

UT-A1 is regulated by vasopressin and is localized to the apical membrane and intracellular compartment of inner medullary collecting duct (IMCD) cells. UT-A3 is also expressed in the IMCD and is regulated by forskolin in heterologous systems. The goal of the present study is to investigate mechanisms by which vasopressin regulates UT-A3 in rat IMCD. In fresh suspensions of rat IMCD, forskolin increases the phosphorylation of UT-A3, similar to UT-A1. Biotinylation studies indicate that UT-A3 is located in the plasma membrane. Forskolin treatment increases the abundance of UT-A3 in the plasma membrane similar to UT-A1. However, these two transporters do not form a complex through a protein-protein interaction, suggesting that transporter function is unique to each protein. While immunohistochemistry localized UT-A3 to the basal and lateral membranes, a majority of the staining was cytosolic. Immunohistochemistry of vasopressin-treated rat kidney sections also localized UT-A3 primarily to the cytosol with basal and lateral membrane staining but also showed some apical membrane staining in some IMCD cells. This suggests that under normal conditions, UT-A3 functions as the basolateral transporter but in a high cAMP environment, the transporter may move from the cytosol to all plasma membranes to increase urea flux in the IMCD. In summary, this study confirms that UT-A3 is located in the inner medullary tip where it is expressed in the basolateral membrane, shows that UT-A3 is a phosphoprotein in rat IMCD that can be trafficked to the plasma membrane independent of UT-A1, and suggests that vasopressin may induce UT-A3 expression in the apical plasma membrane of IMCD.

cAMP; vasopressin; concentrating mechanism; urea transport

This article has been cited by other articles:

				Y. Wang, J. D. Klein, M. A. Blount, C. F. Martin, K. J. Kent, V. Pech, S. M. Wall, and J. M. Sands Epac Regulates UT-A1 to Increase Urea Transport in Inner Medullary Collecting Ducts J. Am. Soc. Nephrol., September 1, 2009; 20(9): 2018 - 2024. [Abstract] [Full Text] [PDF]

				A. C. Mistry, R. Mallick, J. D. Klein, T. Weimbs, J. M. Sands, and O. Frohlich Syntaxin specificity of aquaporins in the inner medullary collecting duct Am J Physiol Renal Physiol, August 1, 2009; 297(2): F292 - F300. [Abstract] [Full Text] [PDF]

				G. S. Stewart, A. Thistlethwaite, H. Lees, G. J. Cooper, and C. Smith Vasopressin regulation of the renal UT-A3 urea transporter Am J Physiol Renal Physiol, March 1, 2009; 296(3): F642 - F648. [Abstract] [Full Text] [PDF]

				Y.-M. Kim, W.-Y. Kim, H.-W. Lee, J. Kim, H. M. Kwon, J. D. Klein, J. M. Sands, and D. Kim Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis Am J Physiol Renal Physiol, January 1, 2009; 296(1): F67 - F77. [Abstract] [Full Text] [PDF]

				N. W. Blessing, M. A. Blount, J. M. Sands, C. F. Martin, and J. D. Klein Urea transporters UT-A1 and UT-A3 accumulate in the plasma membrane in response to increased hypertonicity Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1336 - F1341. [Abstract] [Full Text] [PDF]

				C. Li, W. Wang, S. N. Summer, S. Falk, and R. W. Schrier Downregulation of UT-A1/UT-A3 Is Associated with Urinary Concentrating Defect in Glucocorticoid-Excess State J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1975 - 1981. [Abstract] [Full Text] [PDF]

				G. S. Stewart, J. H. O'Brien, and C. P. Smith Ubiquitination regulates the plasma membrane expression of renal UT-A urea transporters Am J Physiol Cell Physiol, July 1, 2008; 295(1): C121 - C129. [Abstract] [Full Text] [PDF]

				M. A. Blount, A. C. Mistry, O. Frohlich, S. R. Price, G. Chen, J. M. Sands, and J. D. Klein Phosphorylation of UT-A1 urea transporter at serines 486 and 499 is important for vasopressin-regulated activity and membrane accumulation Am J Physiol Renal Physiol, July 1, 2008; 295(1): F295 - F299. [Abstract] [Full Text] [PDF]

				M. A. Blount, J. M. Sands, K. J. Kent, T. D. Smith, S. R. Price, and J. D. Klein Candesartan augments compensatory changes in medullary transport proteins in the diabetic rat kidney Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1448 - F1452. [Abstract] [Full Text] [PDF]