| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland
The luminal uptake of L-cystine and cationic amino acids by (re)absorptive epithelia, as found in the small intestine and the proximal kidney tubule, is mediated by the transport system b0,+, which is defective in cystinuria. Expression studies in Xenopus laevis oocytes and other nonepithelial cells as well as genetic studies on cystinuria patients have demonstrated that two gene products, the glycoprotein rBAT and the multitransmembrane-domain protein b0,+AT, are required for system b0,+ function. To study the biosynthesis, surface expression, polarity, and function of this heterodimer in an epithelial context, we established stable Madin-Darby canine kidney (MDCK) cell lines expressing rBAT and/or b0,+AT. Confocal immunofluorescence microscopy shows that both subunits depend on each other for apical surface expression. Immunoprecipitation of biosynthetically labeled proteins indicates that b0,+AT is stable in the absence of rBAT, whereas rBAT is rapidly degraded in the absence of b0,+AT. When both are coexpressed, they associate covalently and rBAT becomes fully glycosylated and more stable. Functional experiments show that the expressed transport is of the high-affinity b0,+-type and is restricted to the apical side of the epithelia. In conclusion, coexpression experiments in MDCK cell epithelia strongly suggest that the intracellular association of rBAT and b0,+AT is required for the surface expression of either subunit, which together form a functional heterocomplex at the apical cell membrane.
glycoprotein-associated amino acid transporter; cystinuria; exchanger; epithelial cell polarity; kidney transport; intestinal absorption; Madin-Darby canine kidney cells
This article has been cited by other articles:
|
|
 |
|
  P. Bartoccioni, M. Rius, A. Zorzano, M. Palacin, and J. Chillaron Distinct classes of trafficking rBAT mutants cause the type I cystinuria phenotype Hum. Mol. Genet., June 15, 2008; 17(12): 1845 - 1854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Broer Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia Physiol Rev, January 1, 2008; 88(1): 249 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Verrey Does kidney amino acid transport have something to do with blood pressure? Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2449 - 2451. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Palacin, V. Nunes, M. Font-Llitjos, M. Jimenez-Vidal, J. Fort, E. Gasol, M. Pineda, L. Feliubadalo, J. Chillaron, and A. Zorzano The Genetics of Heteromeric Amino Acid Transporters Physiology, April 1, 2005; 20(2): 112 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Font-Llitjos, M Jimenez-Vidal, L Bisceglia, M Di Perna, L de Sanctis, F Rousaud, L Zelante, M Palacin, and V Nunes New insights into cystinuria: 40 new mutations, genotype-phenotype correlation, and digenic inheritance causing partial phenotype J. Med. Genet., January 1, 2005; 42(1): 58 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. I. Closs, A. Simon, N. Vekony, and A. Rotmann Plasma Membrane Transporters for Arginine J. Nutr., October 1, 2004; 134(10): 2752S - 2759S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bauch, N. Forster, D. Loffing-Cueni, V. Summa, and F. Verrey Functional Cooperation of Epithelial Heteromeric Amino Acid Transporters Expressed in Madin-Darby Canine Kidney Cells J. Biol. Chem., January 3, 2003; 278(2): 1316 - 1322. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
