AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (February 20, 2002). doi:10.1152/ajprenal.00333.2001
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
283/1/F150    most recent
00333.2001v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leal-Pinto, E.
Right arrow Articles by Abramson, R. G
Right arrow Search for Related Content
PubMed
Right arrow Articles by Leal-Pinto, E.
Right arrow Articles by Abramson, R. G

Articles in PresS, published online ahead of print February 19, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00333.2001
Submitted on November 1, 2001
Accepted on February 12, 2002

Functional analysis and molecular model of the human urate transporter/channel, hUAT

Edgar Leal-Pinto1, B. Eleazar Cohen2, Michael S Lipkowitz1, and Ruth G Abramson1*

1 Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
2 Division of Extramural Activities, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA

* To whom correspondence should be addressed. E-mail: raBRAMSON{at}smtplink.mssm.EDU.

Recombinant protein, designated hUAT, the human homologue of the rat urate transporter/channel (UAT) functions as a highly selective urate channel in lipid bilayers. Functional analysis indicates that hUAT activity, like UAT, is selectively blocked by oxonate from its cytosolic side whereas pyrazinoate and adenosine selectively block from the channel's extracellular face. Importantly, hUAT is a galectin, a protein with two ß galactoside binding domains that bind lactose. Lactose significantly increased hUAT open probability, but only when added to the channel's extracellular side. This effect on open probability was mimicked by glucose, but not ribose, suggesting a role for extracellular glucose in regulating hUAT channel activity. These functional observations support a four transmembrane domain structural model of hUAT as previously predicted from the primary structure of UAT. hUAT and UAT, however, are not functionally identical: hUAT has a significantly lower single channel conductance and open probability is voltage independent. These differences suggest that evolutionary changes in specific amino acids in these highly homologous proteins are functionally relevant in defining these biophysical properties.




This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
M. Hosoyamada, K. Ichida, A. Enomoto, T. Hosoya, and H. Endou
Function and Localization of Urate Transporter 1 in Mouse Kidney
J. Am. Soc. Nephrol., February 1, 2004; 15(2): 261 - 268.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. Rampoldi, G. Caridi, D. Santon, F. Boaretto, I. Bernascone, G. Lamorte, R. Tardanico, M. Dagnino, G. Colussi, F. Scolari, et al.
Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics
Hum. Mol. Genet., December 15, 2003; 12(24): 3369 - 3384.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.