|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 27, 20676-20684, July 7, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of The differential polarized distribution of the
reduced- folate transporter (RFT-1) and folate receptor
Expression and Differential Polarization of the Reduced-folate
Transporter-1 and the Folate Receptor
in Mammalian Retinal Pigment
Epithelium*
,
,,,**
Cellular Biology and Anatomy,
§ Biochemistry and Molecular Biology, ¶ Obstetrics and
Gynecology, and ** Ophthalmology, Medical College of Georgia,
Augusta, Georgia 30912 and the Program in Molecular
Pharmacology and Experimental Therapeutics, Memorial Sloan-Kettering
Cancer Center and Graduate School of Medical Sciences, Cornell
University, New York, New York 10021
(FR),
the two proteins involved in the transport of folate, has been
characterized in normal mouse retinal pigment epithelium (RPE) and in
cultured human RPE cells. RPE cells mediate the vectorial transfer of
nutrients from choroidal blood to neural retina. Whereas FR is known
to be present in many cell types of the neural retina, in
situ hybridization analysis in the present study demonstrated
that RFT-1 is present only in RPE. Laser-scanning confocal microscopy
using antibodies specific for RFT-1 demonstrated an apical distribution
of this protein in cultured human and intact mouse RPE, which contrasts with the basolateral distribution of FR in these cells. The
expression of RFT-1 in the RPE cell apical membrane was confirmed by
functional studies with purified apical membrane vesicles from bovine
RPE. These studies, done with
N5-methyltetrahydrofolate (the predominant
folate derivative in blood) and folate as substrates, have shown that
RFT-1 functions in a Na+- and C1
-independent
manner. The transporter is specific for folate and its analogs. A
transmembrane H+ gradient influences the transport function
of this protein markedly; the transport mechanism is likely to be
either folate/H+ co-transport or folate/OH
exchange. Based on the differential polarization of FR and RFT-1 in
RPE, we suggest that these two proteins work in a concerted manner to
bring about the vectorial transfer of folate across the RPE cell layer
from the choroidal blood to the neural retina. This constitutes the
first report of the differential polarization of the two folate
transport proteins in any polarized epithelium.
*
This work was supported by National Institutes of Health
Grants HD33347 and EY13089 and by the Medical College of Georgia Research Institute, Fight for Sight-Prevent Blindness America.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Cellular
Biology and Anatomy, CB 2820, Medical College of Georgia, Augusta, GA
30912-2000. Tel.: 706-721-7392; Fax: 706-721-6839; E-mail: sbsmith@mail.mcg.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  T. B. Shafizadeh and C. H. Halsted Postnatal ontogeny of intestinal GCPII and the RFC in pig Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G476 - G481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Bridges, L. Joshee, and R. K. Zalups Multidrug Resistance Proteins and the Renal Elimination of Inorganic Mercury Mediated by 2,3-Dimercaptopropane-1-Sulfonic Acid and Meso-2,3-dimercaptosuccinic Acid J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 383 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. Subramanian, J. S. Marchant, and H. M. Said Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia Am J Physiol Cell Physiol, January 1, 2008; 294(1): C233 - C240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Umapathy, J. P. Gnana-Prakasam, P. M. Martin, B. Mysona, Y. Dun, S. B. Smith, V. Ganapathy, and P. D. Prasad Cloning and Functional Characterization of the Proton-Coupled Electrogenic Folate Transporter and Analysis of Its Expression in Retinal Cell Types Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5299 - 5305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Martin, Y. Dun, B. Mysona, S. Ananth, P. Roon, S. B. Smith, and V. Ganapathy Expression of the Sodium-Coupled Monocarboxylate Transporters SMCT1 (SLC5A8) and SMCT2 (SLC5A12) in Retina Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3356 - 3363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Martin, J. P. Gnana-Prakasam, P. Roon, R. G. Smith, S. B. Smith, and V. Ganapathy Expression and Polarized Localization of the Hemochromatosis Gene Product HFE in Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4238 - 4244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Umapathy, W. Li, B. A. Mysona, S. B. Smith, and V. Ganapathy Expression and Function of Glutamine Transporters SN1 (SNAT3) and SN2 (SNAT5) in Retinal Muller Cells Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 3980 - 3987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M Said, S. Wang, and T. Y Ma Mechanism of riboflavin uptake by cultured human retinal pigment epithelial ARPE-19 cells: possible regulation by an intracellular Ca2+-calmodulin-mediated pathway J. Physiol., July 15, 2005; 566(2): 369 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhao, S. Chattopadhyay, M. Hanscom, and I. D. Goldman Antifolate Resistance in a HeLa Cell Line Associated With Impaired Transport Independent of the Reduced Folate Carrier Clin. Cancer Res., December 15, 2004; 10(24): 8735 - 8742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, R. Zhao, and I. D. Goldman Characterization of a Folate Transporter in HeLa Cells with a Low pH Optimum and High Affinity for Pemetrexed Distinct from the Reduced Folate Carrier Clin. Cancer Res., September 15, 2004; 10(18): 6256 - 6264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hatanaka, M. Haramura, Y.-J. Fei, S. Miyauchi, C. C. Bridges, P. S. Ganapathy, S. B. Smith, V. Ganapathy, and M. E. Ganapathy Transport of Amino Acid-Based Prodrugs by the Na+- and Cl--Coupled Amino Acid Transporter ATB0,+ and Expression of the Transporter in Tissues Amenable for Drug Delivery J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 1138 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhao, F. Gao, M. Hanscom, and I. D. Goldman A Prominent Low-pH Methotrexate Transport Activity in Human Solid Tumors: Contribution to the Preservation of Methotrexate Pharmacologic Activity in HeLa Cells Lacking the Reduced Folate Carrier Clin. Cancer Res., January 15, 2004; 10(2): 718 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Inoue, L. Zhuang, D. M. Maddox, S. B. Smith, and V. Ganapathy Structure, Function, and Expression Pattern of a Novel Sodium-coupled Citrate Transporter (NaCT) Cloned from Mammalian Brain J. Biol. Chem., October 11, 2002; 277(42): 39469 - 39476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Naggar, M. S. Ola, P. Moore, W. Huang, C. C. Bridges, V. Ganapathy, and S. B. Smith Downregulation of Reduced-Folate Transporter by Glucose in Cultured RPE Cells and in RPE of Diabetic Mice Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 556 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Bridges, M. S. Ola, P. D. Prasad, A. El-Sherbeny, V. Ganapathy, and S. B. Smith Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1825 - C1836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rajgopal, E. E. Sierra, R. Zhao, and I. D. Goldman Expression of the reduced folate carrier SLC19A1 in IEC-6 cells results in two distinct transport activities Am J Physiol Cell Physiol, November 1, 2001; 281(5): C1579 - C1586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhao, R. G. Russell, Y. Wang, L. Liu, F. Gao, B. Kneitz, W. Edelmann, and I. D. Goldman Rescue of Embryonic Lethality in Reduced Folate Carrier-deficient Mice by Maternal Folic Acid Supplementation Reveals Early Neonatal Failure of Hematopoietic Organs J. Biol. Chem., March 23, 2001; 276(13): 10224 - 10228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kutty, G. Kutty, W. Samuel, T. Duncan, C. C. Bridges, A. El-Sherbeeny, C. N. Nagineni, S. B. Smith, and B. Wiggert Molecular Characterization and Developmental Expression of NORPEG, a Novel Gene Induced by Retinoic Acid J. Biol. Chem., January 19, 2001; 276(4): 2831 - 2840. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |