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) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirayama, B. A. Articles by Wright, E. M. Search for Related Content PubMed PubMed Citation Articles by Hirayama, B. A. Articles by Wright, E. M. Social Bookmarking                      What's this?

Volume 272, Number 4, Issue of January 24, 1997 pp. 2110-2115
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Cation Effects on Protein Conformation and Transport in the Na⁺/Glucose Cotransporter

(Received for publication, August 9, 1996, and in revised form, October 23, 1996)

From the Department of Physiology, UCLA School of Medicine, Los Angeles, California 90095-1751

Cation-driven cotransporters are essential membrane proteins in procaryotes and eucaryotes, which use the energy of the transmembrane electrochemical gradient to drive transport of a substrate against its concentration gradient. Do they share a common mechanism? Cation selectivity of the rabbit isoform of the Na⁺/glucose cotransporter (SGLT1) was examined using the twoelectrode voltage clamp and the Xenopus oocyte expression system. The effect of H⁺, Li⁺, and Na⁺ on kinetics of SGLT1 was compared to the effects of these cations on the bacterial melibiose. In SGLT1, substitution of H⁺ or Li⁺ for Na⁺ caused a kinetic penalty in that the apparent affinity for sugar (K_0.5^sugar) decreased by an order of magnitude or more (from 0.2 to 30 mM) depending on the membrane potential and cation. The effect of the cation on the K_0.5^sugar/V profiles was independent of the sugar for glucose and -methyl--D-glucose; this profile was maintained for galactose in Li⁺ and Na⁺, but was 2 orders of magnitude higher in H⁺, but the I_max for glucose, galactose, and -methyl--D-glucose in a given cation were identical. Li⁺ supported a lower maximal rate of transport (I_max) than Na⁺ (~80% of I_max^Na), while the I_max in H⁺ was higher than Na⁺ (180% of I_max^Na). Our interpretation of these results and simulations using a six-state mathematical model, are as follows. 1) Binding of the cation causes a conformational change in the sugar binding pocket, the exact conformation being determined by the specific cation. 2) Once the sugar is bound, it is transported at a characteristic rate determined by the cation. 3) Mathematical simulations suggest that the largest contribution to the kinetic variability of both cation and sugar transport is associated with cation binding. Similarity to the effects of cation substitution in MelB suggests that the mechanism of energy coupling has been evolutionarily conserved.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A.-K. Meinild, D. D. F. Loo, S. Skovstrup, U. Gether, and N. MacAulay Elucidating Conformational Changes in the {gamma}-Aminobutyric Acid Transporter-1 J. Biol. Chem., June 12, 2009; 284(24): 16226 - 16235. [Abstract] [Full Text] [PDF]

				M. G. Blanchard, J.-P. Longpre, B. Wallendorff, and J.-Y. Lapointe Measuring ion transport activities in Xenopus oocytes using the ion-trap technique Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1464 - C1472. [Abstract] [Full Text] [PDF]

				L. V. Virkki, J. Biber, H. Murer, and I. C. Forster Phosphate transporters: a tale of two solute carrier families Am J Physiol Renal Physiol, September 1, 2007; 293(3): F643 - F654. [Abstract] [Full Text] [PDF]

				A. Godoy, V. Ormazabal, G. Moraga-Cid, F. A. Zuniga, P. Sotomayor, V. Barra, O. Vasquez, V. Montecinos, L. Mardones, C. Guzman, et al. Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2: ACTIVATION BY SODIUM AND ABSOLUTE DEPENDENCE ON BIVALENT CATIONS J. Biol. Chem., January 5, 2007; 282(1): 615 - 624. [Abstract] [Full Text] [PDF]

				M S Allagui, N Hfaiedh, C Vincent, F Guermazi, J-C Murat, F Croute, and A E. Feki Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment Human and Experimental Toxicology, May 1, 2006; 25(5): 243 - 250. [Abstract] [PDF]

				K. M. Smith, M. D. Slugoski, S. K. Loewen, A. M. L. Ng, S. Y. M. Yao, X.-Z. Chen, E. Karpinski, C. E. Cass, S. A. Baldwin, and J. D. Young The Broadly Selective Human Na+/Nucleoside Cotransporter (hCNT3) Exhibits Novel Cation-coupled Nucleoside Transport Characteristics J. Biol. Chem., July 8, 2005; 280(27): 25436 - 25449. [Abstract] [Full Text] [PDF]

				M. M. Raja, N. K. Tyagi, and R. K. H. Kinne Phlorizin Recognition in a C-terminal Fragment of SGLT1 Studied by Tryptophan Scanning and Affinity Labeling J. Biol. Chem., December 5, 2003; 278(49): 49154 - 49163. [Abstract] [Full Text] [PDF]

				E. M. Wright Renal Na+-glucose cotransporters Am J Physiol Renal Physiol, January 1, 2001; 280(1): F10 - F18. [Abstract] [Full Text] [PDF]

				O. Gal-Garber, S. J. Mabjeesh, D. Sklan, and Z. Uni Partial Sequence and Expression of the Gene for and Activity of the Sodium Glucose Transporter in the Small Intestine of Fed, Starved and Refed Chickens J. Nutr., September 1, 2000; 130(9): 2174 - 2179. [Abstract] [Full Text]

				P. Nalbant, C. Boehmer, L. Dehmelt, F. Wehner, and A. Werner Functional characterization of a Na+-phosphate cotransporter (NaPi-II) from zebrafish and identification of related transcripts J. Physiol., October 1, 1999; 520(1): 79 - 89. [Abstract] [Full Text] [PDF]

				X.-Z. Chen, C. Shayakul, U. V. Berger, W. Tian, and M. A. Hediger Characterization of a Rat Na+-Dicarboxylate Cotransporter J. Biol. Chem., August 14, 1998; 273(33): 20972 - 20981. [Abstract] [Full Text] [PDF]

				A. M. Pajor, B. A. Hirayama, and D. D. F. Loo Sodium and Lithium Interactions with the Na+/Dicarboxylate Cotransporter J. Biol. Chem., July 24, 1998; 273(30): 18923 - 18929. [Abstract] [Full Text] [PDF]

				A-K Meinild, D A Klaerke, D D F Loo, E M Wright, and T Zeuthen The human Na+-glucose cotransporter is a molecular water pump J. Physiol., April 1, 1998; 508(1): 15 - 21. [Abstract] [Full Text] [PDF]

				S. Eskandari, D. D. F. Loo, G. Dai, O. Levy, E. M. Wright, and N. Carrasco Thyroid Na+/I- Symporter. MECHANISM, STOICHIOMETRY, AND SPECIFICITY J. Biol. Chem., October 24, 1997; 272(43): 27230 - 27238. [Abstract] [Full Text] [PDF]

				M. Quick, D. D. F. Loo, and E. M. Wright Neutralization of a Conserved Amino Acid Residue in the Human Na+/Glucose Transporter (hSGLT1) Generates a Glucose-gated H+ Channel J. Biol. Chem., January 12, 2001; 276(3): 1728 - 1734. [Abstract] [Full Text] [PDF]

				D. H. Feldman, W. R. Harvey, and B. R. Stevens A Novel Electrogenic Amino Acid Transporter Is Activated by K+ or Na+, Is Alkaline pH-dependent, and Is Cl--independent J. Biol. Chem., August 4, 2000; 275(32): 24518 - 24526. [Abstract] [Full Text] [PDF]