Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Fry AC, Su Y, Yiu V, Cuthbert AW, Trachtman H, Karet Frankl FE.
???displayArticle.abstract???
Mutations in SLC4A1 that mislocalize its product, the chloride/bicarbonate exchanger AE1, away from its normal position on the basolateral membrane of the α-intercalated cell cause autosomal dominant distal renal tubular acidosis (dRTA). We studied a family exhibiting dominant inheritance and defined a mutation (AE1-M909T) that affects the C terminus of AE1, a region rich in potential targeting motifs that are incompletely characterized. Expression of AE1-M909T in Xenopus oocytes confirmed preservation of its anion exchange function. Wild-type GFP-tagged AE1 localized to the basolateral membrane of polarized MDCK cells, but AE1-M909T localized to both the apical and basolateral membranes. Wild-type AE1 trafficked directly to the basolateral membrane without apical passage, whereas AE1-M909T trafficked to both cell surfaces, implying the gain of an apical-targeting signal. We found that AE1-M909T acquired class 1 PDZ ligand activity that the wild type did not possess. In summary, the AE1-M909T mutation illustrates the role of abnormal targeting in dRTA and provides insight into C-terminal motifs that govern normal trafficking of AE1.
???displayArticle.pubmedLink???
22518001 ???displayArticle.pmcLink???PMC3380654 ???displayArticle.link???J Am Soc Nephrol ???displayArticle.grants???[+]
Alper,
Molecular physiology and genetics of Na+-independent SLC4 anion exchangers.
2009, Pubmed
Alper,
Molecular physiology and genetics of Na+-independent SLC4 anion exchangers.
2009,
Pubmed Anderson,
Transcytosis of NgCAM in epithelial cells reflects differential signal recognition on the endocytic and secretory pathways.
2005,
Pubmed Balkovetz,
Claudins at the gate: determinants of renal epithelial tight junction paracellular permeability.
2006,
Pubmed Beckmann,
An N-terminal GFP tag does not alter the functional expression to the plasma membrane of red cell and kidney anion exchanger (AE1) in mammalian cells.
2002,
Pubmed Brône,
PDZ proteins retain and regulate membrane transporters in polarized epithelial cell membranes.
2005,
Pubmed Brown,
Mitochondria-rich, proton-secreting epithelial cells.
1996,
Pubmed Bruce,
Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells.
2000,
Pubmed
,
Xenbase Bruce,
Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene.
1997,
Pubmed
,
Xenbase Campo,
Molecular mechanisms of membrane polarity in renal epithelial cells.
2005,
Pubmed Casanova,
Direct apical sorting of rat liver dipeptidylpeptidase IV expressed in Madin-Darby canine kidney cells.
1991,
Pubmed Cheidde,
A novel mutation in the anion exchanger 1 gene is associated with familial distal renal tubular acidosis and nephrocalcinosis.
2003,
Pubmed Chu,
Band 3 Edmonton I, a novel mutant of the anion exchanger 1 causing spherocytosis and distal renal tubular acidosis.
2010,
Pubmed
,
Xenbase Cordat,
Unraveling trafficking of the kidney anion exchanger 1 in polarized MDCK epithelial cells.
2006,
Pubmed Cordat,
Carboxyl-terminal truncations of human anion exchanger impair its trafficking to the plasma membrane.
2003,
Pubmed Cowan,
EphB2 guides axons at the midline and is necessary for normal vestibular function.
2000,
Pubmed Devonald,
Non-polarized targeting of AE1 causes autosomal dominant distal renal tubular acidosis.
2003,
Pubmed Ellgaard,
Quality control in the endoplasmic reticulum.
2003,
Pubmed Fam,
P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2.
2005,
Pubmed Farr,
Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells.
2009,
Pubmed Fernández-Larrea,
A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface.
1999,
Pubmed Garcia,
Lysine 539 of human band 3 is not essential for ion transport or inhibition by stilbene disulfonates.
1989,
Pubmed
,
Xenbase Geering,
A role for the beta-subunit in the expression of functional Na+-K+-ATPase in Xenopus oocytes.
1989,
Pubmed
,
Xenbase Girotti,
TGN38-green fluorescent protein hybrid proteins expressed in stably transfected eukaryotic cells provide a tool for the real-time, in vivo study of membrane traffic pathways and suggest a possible role for ratTGN38.
1996,
Pubmed Gisler,
PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.
2003,
Pubmed Grindstaff,
Apiconuclear organization of microtubules does not specify protein delivery from the trans-Golgi network to different membrane domains in polarized epithelial cells.
1998,
Pubmed Groves,
Functional cell surface expression of the anion transport domain of human red cell band 3 (AE1) in the yeast Saccharomyces cerevisiae.
1996,
Pubmed Ihrke,
Apical plasma membrane proteins and endolyn-78 travel through a subapical compartment in polarized WIF-B hepatocytes.
1998,
Pubmed Inaba,
Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation.
1996,
Pubmed Jarolim,
Autosomal dominant distal renal tubular acidosis is associated in three families with heterozygosity for the R589H mutation in the AE1 (band 3) Cl-/HCO3- exchanger.
1998,
Pubmed
,
Xenbase Karet,
Inherited distal renal tubular acidosis.
2002,
Pubmed Karet,
Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis.
1998,
Pubmed Kaufman,
Up-regulation of the homophilic adhesion molecule sidekick-1 in podocytes contributes to glomerulosclerosis.
2010,
Pubmed Keller,
Post-Golgi biosynthetic trafficking.
1997,
Pubmed Killisch,
Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome.
1992,
Pubmed Kocher,
Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains.
1998,
Pubmed Kollert-Jöns,
Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in its NH2 terminus.
1993,
Pubmed Le Panse,
Antibodies to the 280-kd coated pit protein, target of teratogenic antibodies, produce alterations in the traffic of internalized proteins.
1994,
Pubmed MacVinish,
Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR.
2007,
Pubmed Maday,
A PDZ-binding motif controls basolateral targeting of syndecan-1 along the biosynthetic pathway in polarized epithelial cells.
2008,
Pubmed Mostov,
Membrane traffic in polarized epithelial cells.
2000,
Pubmed Nolan,
Antibody to the phosphomannosyl receptor inhibits recycling of receptor in fibroblasts.
1987,
Pubmed NULL,
Unravelling of the molecular mechanisms of kidney stones. Report of a Meeting of Physicians and Scientists.
1996,
Pubmed Praetor,
Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells.
1999,
Pubmed Quilty,
Impaired trafficking of distal renal tubular acidosis mutants of the human kidney anion exchanger kAE1.
2002,
Pubmed Ramsey,
Serotonin transporter function and pharmacology are sensitive to expression level: evidence for an endogenous regulatory factor.
2002,
Pubmed
,
Xenbase Ribeiro,
Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3.
2000,
Pubmed Richardson,
Identification of two strains of MDCK cells which resemble separate nephron tubule segments.
1981,
Pubmed Rodriguez-Boulan,
Organization of vesicular trafficking in epithelia.
2005,
Pubmed Rungroj,
A novel missense mutation in AE1 causing autosomal dominant distal renal tubular acidosis retains normal transport function but is mistargeted in polarized epithelial cells.
2004,
Pubmed
,
Xenbase Smythe,
Monoclonal antibodies recognizing epitopes on the extracellular face and intracellular N-terminus of the human erythrocyte anion transporter (band 3) and their application to the analysis of South East Asian ovalocytes.
1995,
Pubmed Su,
Glyceraldehyde 3-phosphate dehydrogenase is required for band 3 (anion exchanger 1) membrane residency in the mammalian kidney.
2011,
Pubmed Tanemoto,
MAGI-1a functions as a scaffolding protein for the distal renal tubular basolateral K+ channels.
2008,
Pubmed Thomson,
Role of PDZK1 in membrane expression of renal brush border ion exchangers.
2005,
Pubmed Toye,
Band 3 Walton, a C-terminal deletion associated with distal renal tubular acidosis, is expressed in the red cell membrane but retained internally in kidney cells.
2002,
Pubmed
,
Xenbase Toye,
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).
2004,
Pubmed Williamson,
Human kidney anion exchanger 1 localisation in MDCK cells is controlled by the phosphorylation status of two critical tyrosines.
2008,
Pubmed Wu,
Anion exchanger 1 interacts with nephrin in podocytes.
2010,
Pubmed
,
Xenbase Yu,
A bipartite signal regulates the faithful delivery of apical domain marker podocalyxin/Gp135.
2007,
Pubmed
