spacer gif spacer gif spacer gif spacer gif Propose a workshop for 2011 spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 2 Mar 2004
doi: 10.1242/jcs.00974

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.00974v1
117/8/1399    most recent
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 Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Toye, A. M.
Right arrow Articles by Tanner, M. J.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toye, A. M.
Right arrow Articles by Tanner, M. J.A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

Regions of human kidney anion exchanger 1 (kAE1) required for basolateral targeting of kAE1 in polarised kidney cells: mis-targeting explains dominant renal tubular acidosis (dRTA)


Ashley M. Toye*, George Banting, and Michael J.A. Tanner
* Author for correspondence (e-mail: ash.m.toye{at}bristol.ac.uk)

Distal renal tubular acidosis (dRTA) is characterised by defective acid secretion by kidney {alpha}-intercalated cells. Some dominantly inherited forms of dRTA result from anion exchanger 1 (AE1) mutations. We have developed a stably transfected cell model for the expression of human kidney AE1 (kAE1) and mutant kAE1 proteins in MDCKI cells. Normal kAE1 was delivered to the plasma membrane of non-polarised cells and to the basolateral membrane of polarised cells. The AE1 N-glycan was processed to a complex form. Surprisingly, expression of kAE1 increased the permeability of the paracellular barrier of polarised MDCKI monolayers. All dominant dRTA mutations examined altered the targeting of kAE1 in MDCKI cells. The mutant proteins kAE1(R589H), kAE1(S613F) and kAE1(R901Stop) were retained in the ER in non-polarised cells, but the kAE1(R901Stop) protein was also present in late endosomes/lysosomes. The complex N-glycan of kAE1(R901Stop) was larger than that of normal kAE1. In polarised cells, the mutant kAE1(R901Stop) was mis-targeted to the apical membrane, while the kAE1(R589H) and kAE1(S613F) mutants did not reach the cell surface. These results demonstrate that dominant dRTA mutations cause aberrant targeting of kAE1 in polarised kidney cells and provide an explanation for the origin of dominant dRTA. Our data also demonstrate that the 11 C-terminal residues of kAE1 contain a tyrosine-dependent basolateral targeting signal that is not recognised by µ1B-containing AP-1 adaptor complexes. In the absence of the N-terminus of kAE1, the C-terminus was not sufficient to localise kAE1 to the basolateral membrane. These results suggest that a determinant within the kAE1 N-terminus co-operates with the C-terminus for kAE1 basolateral localisation.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Exp. Biol.Home page
S. L. Alper
Molecular physiology and genetics of Na+-independent SLC4 anion exchangers
J. Exp. Biol., June 1, 2009; 212(11): 1672 - 1683.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. C. N. Brown, D. Hallouane, W. J. Mawby, F. E. Karet, M. A. Saleem, A. J. Howie, and A. M. Toye
RhCG is the major putative ammonia transporter expressed in the human kidney, and RhBG is not expressed at detectable levels
Am J Physiol Renal Physiol, June 1, 2009; 296(6): F1279 - F1290.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
R. C. Williamson, A. C. N. Brown, W. J. Mawby, and A. M. Toye
Human kidney anion exchanger 1 localisation in MDCK cells is controlled by the phosphorylation status of two critical tyrosines
J. Cell Sci., October 15, 2008; 121(20): 3422 - 3432.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Sohet, Y. Colin, S. Genetet, P. Ripoche, S. Metral, C. Le Van Kim, and C. Lopez
Phosphorylation and Ankyrin-G Binding of the C-terminal Domain Regulate Targeting and Function of the Ammonium Transporter RhBG
J. Biol. Chem., September 26, 2008; 283(39): 26557 - 26567.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
S. Walsh, F. Borgese, N. Gabillat, R. Unwin, and H. Guizouarn
Cation transport activity of anion exchanger 1 mutations found in inherited distal renal tubular acidosis
Am J Physiol Renal Physiol, August 1, 2008; 295(2): F343 - F350.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. M. Toye, R. C. Williamson, M. Khanfar, B. Bader-Meunier, T. Cynober, M. Thibault, G. Tchernia, M. Dechaux, J. Delaunay, and L. J. Bruce
Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild-type band 3 and glycophorin A
Blood, June 1, 2008; 111(11): 5380 - 5389.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Keskanokwong, H. J. Shandro, D. E. Johnson, S. Kittanakom, G. L. Vilas, P. Thorner, R. A. F. Reithmeier, V. Akkarapatumwong, P.-t. Yenchitsomanus, and J. R. Casey
Interaction of Integrin-linked Kinase with the Kidney Chloride/Bicarbonate Exchanger, kAE1
J. Biol. Chem., August 10, 2007; 282(32): 23205 - 23218.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
A. C. Fry and F. E. Karet
Inherited Renal Acidoses
Physiology, June 1, 2007; 22(3): 202 - 211.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. A. Stehberger, B. E. Shmukler, A. K. Stuart-Tilley, L. L. Peters, S. L. Alper, and C. A. Wagner
Distal Renal Tubular Acidosis in Mice Lacking the AE1 (Band3) Cl-/HCO3- Exchanger (slc4a1)
J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1408 - 1418.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
S. Walsh, C. M. Turner, A. Toye, C. Wagner, P. Jaeger, C. Laing, and R. Unwin
Immunohistochemical comparison of a case of inherited distal renal tubular acidosis (with a unique AE1 mutation) with an acquired case secondary to autoimmune disease
Nephrol. Dial. Transplant., March 1, 2007; 22(3): 807 - 812.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. M. Piermarini, E. Y. Kim, and W. F. Boron
Evidence against a Direct Interaction between Intracellular Carbonic Anhydrase II and Pure C-terminal Domains of SLC4 Bicarbonate Transporters
J. Biol. Chem., January 12, 2007; 282(2): 1409 - 1421.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
E. Cordat and R. A. F. Reithmeier
Expression and interaction of two compound heterozygous distal renal tubular acidosis mutants of kidney anion exchanger 1 in epithelial cells
Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1354 - F1361.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. M. Toye, M. D. Parker, C. M. Daly, J. Lu, L. V. Virkki, M. F. Pelletier, and W. F. Boron
The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia
Am J Physiol Cell Physiol, October 1, 2006; 291(4): C788 - C801.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
D. J. D. Espiritu, A. A. Bernardo, and J. A. L. Arruda
Role of NH2 and COOH termini in targeting, stability, and activity of sodium bicarbonate cotransporter 1
Am J Physiol Renal Physiol, September 1, 2006; 291(3): F588 - F596.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
S. L Alper
Molecular physiology of SLC4 anion exchangers
Exp Physiol, January 1, 2006; 91(1): 153 - 161.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A.-D. Qi, S. C. Wolff, and R. A. Nicholas
The Apical Targeting Signal of the P2Y2 Receptor Is Located in Its First Extracellular Loop
J. Biol. Chem., August 12, 2005; 280(32): 29169 - 29175.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. C. Li, P. Szigligeti, R. T. Worrell, J. B. Matthews, L. Conforti, and M. Soleimani
Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis
Am J Physiol Renal Physiol, July 1, 2005; 289(1): F61 - F71.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Lopez, S. Metral, D. Eladari, S. Drevensek, P. Gane, R. Chambrey, V. Bennett, J.-P. Cartron, C. Le Van Kim, and Y. Colin
The Ammonium Transporter RhBG: REQUIREMENT OF A TYROSINE-BASED SIGNAL AND ANKYRIN-G FOR BASOLATERAL TARGETING AND MEMBRANE ANCHORAGE IN POLARIZED KIDNEY EPITHELIAL CELLS
J. Biol. Chem., March 4, 2005; 280(9): 8221 - 8228.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. C. Li, R. T. Worrell, J. B. Matthews, H. Husseinzadeh, L. Neumeier, S. Petrovic, L. Conforti, and M. Soleimani
Identification of a Carboxyl-terminal Motif Essential for the Targeting of Na+-HCO-3 Cotransporter NBC1 to the Basolateral Membrane
J. Biol. Chem., October 8, 2004; 279(41): 43190 - 43197.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Kittanakom, E. Cordat, V. Akkarapatumwong, P.-t. Yenchitsomanus, and R. A. F. Reithmeier
Trafficking Defects of a Novel Autosomal Recessive Distal Renal Tubular Acidosis Mutant (S773P) of the Human Kidney Anion Exchanger (kAE1)
J. Biol. Chem., September 24, 2004; 279(39): 40960 - 40971.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004