Chapter 13 Structure of the erythrocyte band 3 anion exchanger

Reithmeier, Reinhart A.F.; Chan, Siu-Hong; Popov, M.

doi:10.1016/s1383-8121(96)80054-6

Cited by 23 publications

(22 citation statements)

References 154 publications

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“…N-glycan-linked glycosylation site of residues Nx[S/T] (with x being any amino acid residue except P) (Gavel and von Heijne, 1990), exhibiting residues NPT (at N660) rather than the corresponding NSS (at N642) of human AE1, to which an N-glycan chain is attached (Reithmeier et al, 1996). The absence of processing with increasing sizes of newly synthesized proteins during the chase period (Figs 1, 4 and 6) supported this idea.…”

Section: Journal Of Cell Science 119 (17)mentioning

confidence: 79%

“…AE1 (anion exchanger 1, band 3), with apparent molecular masses of 95-105 kDa, is the most abundant transmembrane protein in mammalian red blood cells, accounting for about 25% of the total red-cell membrane proteins (Reithmeier et al, 1996;Tanner, 1997). The N-terminal cytoplasmic domain functions in maintaining mechanical properties of red-cell membranes by attaching the spectrin-actin membrane skeleton to the lipid bilayer through association with ankyrin (Low et al, 1991;Michaely and Bennet, 1995;Zhang et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle

Ito

Koshino

Arashiki

et al. 2006

Journal of Cell Science

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Various mutations in the AE1 (anion exchanger 1, band 3) gene cause dominant hereditary spherocytosis, a common congenital hemolytic anemia associated with deficiencies of AE1 of different degrees and loss of mutant protein from red blood cell membranes. To determine the mechanisms underlying decreases in AE1 protein levels, we employed K562 and HEK293 cell lines and Xenopus oocytes together with bovine wild-type AE1 and an R664X nonsense mutant responsible for dominant hereditary spherocytosis to analyze protein expression, turnover, and intracellular localization. R664X-mutant protein underwent rapid degradation and caused specifically increased turnover and impaired trafficking to the plasma membrane of the wild-type protein through hetero-oligomer formation in K562 cells. Consistent with those observations, co-expression of mutant and wild-type AE1 reduced anion transport by the wild-type protein in oocytes. Transfection studies in K562 and HEK293 cells revealed that the major pathway mediating degradation of both R664X and wild-type AE1 employed endoplasmic reticulum (ER)-associated degradation through the proteasomal pathway. Proteasomal degradation of R664X protein appeared to be independent of both ubiquitylation and N-glycosylation, and aggresome formation was not observed following proteasome inhibition. These findings indicate that AE1 R664X protein, which is associated with dominant hereditary spherocytosis, has a dominant-negative effect on the expression of wild-type AE1

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Section: Journal Of Cell Science 119 (17)mentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle

Ito

Koshino

Arashiki

et al. 2006

Journal of Cell Science

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“…Although slight variations were seen, in all cases there was a sharp N-glycosylation boundary and reasonable agreement with the '12'/14 rule'. AE1 TMs 7 and 8 ( Figure 1) are clearly defined by a hydrophobic stretch of about 20 amino acids each, from Val604 Á/ Ile624 and Met663 Á/Gln683, respectively (Reithmeier 1996). In scanning N-glycosylation of EC4 expressed in a cell-free system, it was found that the first positions to be glycosylated, counting from the lumenal end of TMs 7 and 8, were 637 and 648, respectively (Popov et al 1997).…”

Section: Discussionmentioning

confidence: 99%

“…AE1 is expressed in the erythrocyte membrane, where it carries out the electroneutral exchange of bicarbonate and chloride ions, a process important for increasing the carbon dioxide-carrying capacity of blood. Human AE1 protein consists of 911 amino acids, which forms two domains (Lux et al 1989, Reithmeier et al 1996, Tanner 1993, Tanner et al 1988. The Nterminal cytosolic domain provides anchor sites between the red cell membrane and the underlying cytoskeleton and binds cytosolic proteins such as hemoglobin and glycolytic enzymes (Low 1986).…”

Section: Introductionmentioning

confidence: 99%

Membrane integration and topology of the first transmembrane segment in normal and Southeast Asian ovalocytosis human erythrocyte anion exchanger 1

Cheung

Reithmeier

2005

Molecular Membrane Biology

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Anion exchanger 1 (AE1, or Band 3) is an integral membrane glycoprotein found in erythrocytes, responsible for the electroneutral exchange of chloride and bicarbonate ions across the plasma membrane. Southeast Asian ovalocytosis (SAO) results from a nine-amino acid deletion in the first transmembrane segment (TM) of the AE1 protein that abolishes its transport function. The effects of the SAO deletion on: (1) the efficiency of integration of TM1 into the membrane, and (2) the precise positioning of TM1 relative to the membrane were investigated using scanning N-glycosylation mutagenesis in a cell-free transcription/translation system and in transfected HEK293 cells. AE1 or SAO constructs containing either the endogenous N-glycosylation site at Asn642 in extracellular loop 4 (EC4) or single N-glycosylation sites engineered into an expanded extracellular loop 1 (EC1) were used. N-glycosylation efficiency of EC1 in the SAO construct was significantly lower than that of the AE1 construct, indicating that the SAO deletion impairs membrane integration of TM1 and the translocation of EC1 across the membrane. Scanning N-glycosylation mapping of EC1 in the cell-free system and in transfected cells showed that the C-terminus of both AE1 and SAO TM1 were at the same position relative to the membrane. Thus, the SAO deletion is likely to cause a pulling-in of the polar amino acid sequence immediately N-terminal to the deletion into the lipid bilayer, allowing SAO TM1 that was inserted to assume a transmembrane disposition.

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“…Considerable data are available concerning the topology of the AE1 membrane domain. The topology of the first eight transmembrane segments (TMs ; these are numbered according to the folding model presented in Figure 1) is well defined [5][6][7], whereas controversial topology models containing non-helical membrane-spanning segments have been proposed for the C-terminal region of the TM domain [6,8]. Mutagenesis studies indicate that TM8 of AE1 may form part of the aniontranslocation channel [9].…”

Section: Introductionmentioning

confidence: 99%

Cysteine-directed cross-linking localizes regions of the human erythrocyte anion-exchange protein (AE1) relative to the dimeric interface

Taylor

Zhu

Casey

2001

Biochemical Journal

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The human erythrocyte anion-exchanger isoform 1 (AE1) is a dimeric membrane protein that exchanges chloride for bicarbonate across the erythrocyte plasma membrane. Crystallographic studies suggest that the transmembrane anion channel lies at the interface between the two monomers, whereas kinetic analysis provides evidence that each monomer contains an anion channel. We have studied the structure-function relationship of residues at the dimeric interface of AE1 by cysteine-directed cross-linking. Single cysteine mutations were introduced in 16 positions of putative loop regions throughout AE1. The ability of these residues to be chemically cross-linked to their partner within the dimeric protein complex was assessed by mobility of the protein on immunoblots. Introduced cysteine residues in extracellular loops (ECs) 1-4 and intracellular loop 1 formed

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Chapter 13 Structure of the erythrocyte band 3 anion exchanger

Cited by 23 publications

References 154 publications

Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle

Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle

Membrane integration and topology of the first transmembrane segment in normal and Southeast Asian ovalocytosis human erythrocyte anion exchanger 1

Cysteine-directed cross-linking localizes regions of the human erythrocyte anion-exchange protein (AE1) relative to the dimeric interface

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