ABCB6 is dispensable for erythropoiesis and specifies the new blood group system Langereis

Helias, Virginie; Saison, Carole; Ballif, Bryan A.; Peyrard, Thierry; Takahashi, Jun; Takahashi, Hideo; Tanaka, Mitsunobu; Deybach, Jean‐Charles; Puy, Hervé; Gall, Maude Le; Sureau, Camille; Pham, Bach-Nga; Pennec, Pierre‐Yves Le; Tani, Yoshihiko; Cartron, Jean‐Pierre; Arnaud, Lionel

doi:10.1038/ng.1069

Cited by 129 publications

(184 citation statements)

References 18 publications

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“…Confocal microscopy analysis showed that ABCB6 was expressed at the RBC membrane, and colocalized in some membrane regions with CD55 (Decay Accelerating Factor bearing the Cromer blood group system) (Fig. 3C), in agreement with the recently published results [21]. We further confirmed ABCB6 localization in the red cell membrane by substantial colocalization with glycophorin A in control red cells (Fig.…”

Section: Structural Modeling Of Wild-type and Mutant Abcb6supporting

confidence: 92%

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Missense mutations in the ABCB6 transporter cause dominant familialpseudohyperkalemia

et al. 2012

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Familial Pseudohyperkalemia (FP) is a dominant red cell trait characterized by increased serum [K 1 ] in whole blood stored at or below room temperature, without additional hematological abnormalities. Functional gene mapping and sequencing analysis of the candidate genes within the 2q35-q36 critical interval identified-in 20 affected individuals among three multigenerational FP families-two novel heterozygous missense mutations in the ABCB6 gene that cosegregated with disease phenotype. The two genomic substitutions altered two adjacent nucleotides within codon 375 of ABCB6, a porphyrin transporter that, in erythrocyte membranes, bears the Langereis blood group antigen system. The ABCB6 R375Q mutation did not alter the levels of mRNA or protein, or protein localization in mature erythrocytes or erythroid precursor cells, but it is predicted to modestly alter protein structure. ABCB6 mRNA and protein levels increase during in vitro erythroid differentiation of CD34 1 erythroid precursors and the erythroleukemia cell lines HEL and K562. These data suggest that the two missense mutations in residue 375 of the ABCB6 polypeptide found in affected individuals of families with chromosome 2-linked FP could contribute to the red cell K 1 leak characteristic of this condition. Am. J. Hematol. 88:66-72, 2013. V

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Section: Structural Modeling Of Wild-type and Mutant Abcb6supporting

confidence: 92%

“…This protein was recently identified in the RBC membrane [20], where it displays the Langereis blood group [21].…”

Section: Introductionmentioning

confidence: 97%

Missense mutations in the ABCB6 transporter cause dominant familialpseudohyperkalemia

et al. 2012

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“…57 Moreover, in erythrocyte membranes it bears the Langereis (Lan) blood group antigen system. 58,59 ABCB6 expression increases during erythroid differentiation of CD34+ cells. 56 The ABCB6 missense mutations in FP does not alter mRNA or protein levels, or subcellular localization in mature erythrocytes or erythroid precursor cells, but are predicted to have a pathogenic consequence on protein function.…”

Section: Familial Pseudohyperkalemia and Cryohydrocytosismentioning

confidence: 99%

New insights on hereditary erythrocyte membrane defects

et al. 2016

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© Ferrata Storti Foundationmary role in the removal of aged RBCs. In order to perform these journeys RBCs must possess and maintain a significant deformability. The main author of this property is certainly the membrane, that ensures both mechanical stability and deformability. After the first proposed model of the RBC membrane skeleton 36 years ago, 1 containing the core elements of the modern model, many additional proteins have been discovered during the intervening decades, and their structures and interactions have been defined. RBC membrane structure has been extensively covered by excellent reviews.2,3 Herein we summarize the main concepts. RBC membrane is composed by a fluid double layer of lipids in which approximately 20 major proteins and at least 850 minor ones are embedded. 4 The membrane is attached to an intracellular cytoskeleton by protein-protein and lipid-protein interactions that confer the erythrocyte shape, stability and deformability. The transmembrane proteins have mainly a transporter function. However, several of these also have a structural function, usually performed by an intracytoplasmic domain interacting with cytoskeletal proteins.The lipid bilayer acts as a barrier for the retention of cations and anions within the red cells, while it allows water molecules to pass through freely. Human erythrocytes have high intracellular K + and low intracellular Na + contents when compared with the corresponding ion concentrations in the plasma. The maintenance of this cation gradient between the cell and its environment involves a passive outward movement of K + , which is pumped back by the action of an ATP-dependent Na + /K + pump in exchange for Na+ ions. This protein belongs to a class of transmembrane proteins with a transport function (Figure 1). The third and more important component of the RBC membrane is the cytoskeleton, a protein network that laminates the inner surface of the membrane. Spectrin aand β-chains, proteins 4.1, or 4.1R, and actin are the main components of this skeleton, maintaining the biconcave shape of the RBC. These components are connected to each other in two protein complexes; ankyrin and protein 4.1 complex. The former is composed by band 3 tetramers, Rh, RhAG, CD47, glycophorin A and protein 4.2. Whereas the protein 4.1 complex is composed by band 3 dimers binding adducins a-and β-, glycophorin C, GLUT1 and stomatin (Figure 1). The ends of spectrin tetramers converge toward a protein 4.1 complex (junctional complex). Electron microscopy (EM) shows that this latter links the tail of six spectrin tetramers, forming a pseudo-hexagonal arrangement. 5Spectrin tetramers include anion transporters (band 3 or chloride/bicarbonate exchange). The capability of these transporters to form aggregates could define the half-life of RBCs, causing antibody binding and removal by the spleen. Defects that interrupt this vertical structure (spectrin-actin interaction) underlie the biochemical and molecular basis of hereditary spherocytosis (HS), whereas defects in horizo...

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“…31 However, in two more recent studies, several individuals homozygous for deleterious loss of function mutations, including frameshift and nonsense mutations, were found to have a newly identified rare Lan blood group antigen. There were no reports of coloboma or eye defects in individuals homozygous or heterozygous for these variants 32 . In our family (Family 10), the unaffected father also carried ABCB6, c.575G4A (p.(Arg192Gln)) in the heterozygous state, indicating that this is a variant with incomplete penetrance and that other factor/s are contributing to the disease phenotype in Patient 10.…”

Section: Exome and Target Region Analysismentioning

confidence: 99%

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC, PAX6 and CYP1B1

et al. 2013

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Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods. We used whole-exome sequencing in 11 unrelated developmental eye disease patients, as it provides a strategy for assessment of multiple disease genes simultaneously. We identified five causative variants in four patients in four different disease genes, GJA8, CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients where clinical testing is frequently not undertaken due to lack of availability and cost. The results affected clinical management in all cases. These variants were detected in the cataract/microcornea and Peters anomaly patients. In two patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified with incomplete penetrance, highlighting the complex inheritance pattern associated with this phenotype. In the coloboma/microphthalmia patients, four other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene to be considered as a modifier in coloboma/ microphthalmia.

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ABCB6 is dispensable for erythropoiesis and specifies the new blood group system Langereis

Cited by 129 publications

References 18 publications

Missense mutations in the ABCB6 transporter cause dominant familialpseudohyperkalemia

Missense mutations in the ABCB6 transporter cause dominant familialpseudohyperkalemia

New insights on hereditary erythrocyte membrane defects

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC, PAX6 and CYP1B1

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