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Wu F
,
Saleem MA
,
Kampik NB
,
Satchwell TJ
,
Williamson RC
,
Blattner SM
,
Ni L
,
Toth T
,
White G
,
Young MT
,
Parker MD
,
Alper SL
,
Wagner CA
,
Toye AM
.
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The central role of the multifunctional protein nephrin within the macromolecular complex forming the glomerular slit diaphragm is well established, but the mechanisms linking the slit diaphragm to the cytoskeleton and to the signaling pathways involved in maintaining the integrity of the glomerular filter remain incompletely understood. Here, we report that nephrin interacts with the bicarbonate/chloride transporter kidneyanion exchanger 1 (kAE1), detected by yeast two-hybrid assay and confirmed by immunoprecipitation and co-localization studies. We confirmed low-level glomerular expression of kAE1 in human and mouse kidneys by immunoblotting and immunofluorescence microscopy. We observed less kAE1 in human glomeruli homozygous for the NPHS1(FinMaj) nephrin mutation, whereas kAE1 expression remained unchanged in the collecting duct. We could not detect endogenous kAE1 expression in NPHS1(FinMaj) podocytes in primary culture, but heterologous re-introduction of wild-type nephrin into these podocytes rescued kAE1 expression. In kidneys of Ae1(-/-) mice, nephrin abundance was normal but its distribution was altered along with the reported kAE1-binding protein integrin-linked kinase (ILK). Ae1(-/-) mice had increased albuminuria with glomerular enlargement, mesangial expansion, mesangiosclerosis, and expansion of the glomerular basement membrane. Glomeruli with ILK-deficient podocytes also demonstrated altered AE1 and nephrin expression, further supporting the functional interdependence of these proteins. These data suggest that the podocyte protein kAE1 interacts with nephrin and ILK to maintain the structure and function of the glomerular basement membrane.
Akel,
Enhanced suicidal death of erythrocytes from gene-targeted mice lacking the Cl-/HCO(3)(-) exchanger AE1.
2007, Pubmed
Akel,
Enhanced suicidal death of erythrocytes from gene-targeted mice lacking the Cl-/HCO(3)(-) exchanger AE1.
2007,
Pubmed
Alper,
Molecular physiology of SLC4 anion exchangers.
2006,
Pubmed
,
Xenbase
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
Blasutig,
Phosphorylated YDXV motifs and Nck SH2/SH3 adaptors act cooperatively to induce actin reorganization.
2008,
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
Cordat,
Carboxyl-terminal truncations of human anion exchanger impair its trafficking to the plasma membrane.
2003,
Pubmed
Coward,
Nephrin is critical for the action of insulin on human glomerular podocytes.
2007,
Pubmed
Coward,
Nephrotic plasma alters slit diaphragm-dependent signaling and translocates nephrin, Podocin, and CD2 associated protein in cultured human podocytes.
2005,
Pubmed
Dai,
Essential role of integrin-linked kinase in podocyte biology: Bridging the integrin and slit diaphragm signaling.
2006,
Pubmed
De Paepe,
The transgenic SAD mouse: a model of human sickle cell glomerulopathy.
1994,
Pubmed
El-Aouni,
Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis.
2006,
Pubmed
Fukasawa,
Slit diaphragms contain tight junction proteins.
2009,
Pubmed
GLAUERT,
A new embedding medium for electron microscopy.
1956,
Pubmed
Gerke,
NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is cleaved from podocytes by metalloproteinases.
2005,
Pubmed
Gerke,
Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1.
2003,
Pubmed
Graham,
A new technique for the assay of infectivity of human adenovirus 5 DNA.
1973,
Pubmed
Groves,
Glycophorin A facilitates the expression of human band 3-mediated anion transport in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Harita,
Neph1, a component of the kidney slit diaphragm, is tyrosine-phosphorylated by the Src family tyrosine kinase and modulates intracellular signaling by binding to Grb2.
2008,
Pubmed
Hassoun,
Targeted inactivation of murine band 3 (AE1) gene produces a hypercoagulable state causing widespread thrombosis in vivo.
1998,
Pubmed
Hazen-Martin,
Immunocytochemistry of band 3 protein in kidney and other tissues of control and cystic fibrosis patients.
1987,
Pubmed
Holthöfer,
Nephron segment and cell-type specific expression of gangliosides in the developing and adult kidney.
1994,
Pubmed
Holzman,
Nephrin localizes to the slit pore of the glomerular epithelial cell.
1999,
Pubmed
Huber,
Interaction with podocin facilitates nephrin signaling.
2001,
Pubmed
Jones,
Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes.
2006,
Pubmed
Kanasaki,
Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.
2008,
Pubmed
Keskanokwong,
Interaction of integrin-linked kinase with the kidney chloride/bicarbonate exchanger, kAE1.
2007,
Pubmed
Kestilä,
Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome.
1998,
Pubmed
Kollert-Jöns,
Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in its NH2 terminus.
1993,
Pubmed
LOWRY,
Protein measurement with the Folin phenol reagent.
1951,
Pubmed
Legate,
ILK, PINCH and parvin: the tIPP of integrin signalling.
2006,
Pubmed
Lehtonen,
Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin.
2004,
Pubmed
Lehtonen,
Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex.
2005,
Pubmed
Lehtonen,
CD2-associated protein directly interacts with the actin cytoskeleton.
2002,
Pubmed
Peters,
Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton.
1996,
Pubmed
Putaala,
The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death.
2001,
Pubmed
Qin,
Phosphorylation of nephrin triggers its internalization by raft-mediated endocytosis.
2009,
Pubmed
REYNOLDS,
The use of lead citrate at high pH as an electron-opaque stain in electron microscopy.
1963,
Pubmed
Reiser,
TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function.
2005,
Pubmed
Reiser,
The glomerular slit diaphragm is a modified adherens junction.
2000,
Pubmed
Ribeiro,
Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3.
2000,
Pubmed
SABATINI,
Cytochemistry and electron microscopy. The preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation.
1963,
Pubmed
STEMPAK,
AN IMPROVED STAINING METHOD FOR ELECTRON MICROSCOPY.
1964,
Pubmed
Sachs,
Kidney failure in mice lacking the tetraspanin CD151.
2006,
Pubmed
Saleem,
The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells.
2008,
Pubmed
Saleem,
A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression.
2002,
Pubmed
Schwarz,
Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin.
2001,
Pubmed
Shih,
Congenital nephrotic syndrome in mice lacking CD2-associated protein.
1999,
Pubmed
Shih,
CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain.
2001,
Pubmed
Stehberger,
Distal renal tubular acidosis in mice lacking the AE1 (band3) Cl-/HCO3- exchanger (slc4a1).
2007,
Pubmed
Sterling,
A transport metabolon. Functional interaction of carbonic anhydrase II and chloride/bicarbonate exchangers.
2001,
Pubmed
Tanner,
Band 3 anion exchanger and its involvement in erythrocyte and kidney disorders.
2002,
Pubmed
Tanphaichitr,
Novel AE1 mutations in recessive distal renal tubular acidosis. Loss-of-function is rescued by glycophorin A.
1998,
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
Toye,
Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild-type band 3 and glycophorin A.
2008,
Pubmed
,
Xenbase
Toye,
Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia.
2005,
Pubmed
,
Xenbase
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
Tryggvason,
Hereditary proteinuria syndromes and mechanisms of proteinuria.
2006,
Pubmed
Verma,
Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization.
2006,
Pubmed
Wainwright,
Monoclonal antibodies to the membrane domain of the human erythrocyte anion transport protein. Localization of the C-terminus of the protein to the cytoplasmic side of the red cell membrane and distribution of the protein in some human tissues.
1989,
Pubmed
Walsh,
Immunohistochemical comparison of a case of inherited distal renal tubular acidosis (with a unique AE1 mutation) with an acquired case secondary to autoimmune disease.
2007,
Pubmed
Wartiovaara,
Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography.
2004,
Pubmed
Williamson,
Glycophorin A: Band 3 aid.
2008,
Pubmed
Williamson,
Human kidney anion exchanger 1 localisation in MDCK cells is controlled by the phosphorylation status of two critical tyrosines.
2008,
Pubmed
Winn,
A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis.
2005,
Pubmed
Wu,
Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes.
2001,
Pubmed
Yang,
A mouse model for beta 0-thalassemia.
1995,
Pubmed
Young,
Distinct regions of human glycophorin A enhance human red cell anion exchanger (band 3; AE1) transport function and surface trafficking.
2003,
Pubmed
,
Xenbase
