Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

Kiss, Katalin; Brózik, Anna; Kucsma, Nóra; Toth, Alexandra; Gera, Melinda; Berry, Laurence; Vallentin, Alice; Vial, Henri; Vidal, Michel; Szakács, Gergely

doi:10.1371/journal.pone.0037378

Cited by 84 publications

(99 citation statements)

References 63 publications

(91 reference statements)

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“…Lan blood group mismatch can cause hemolytic transfusion reactions and hemolytic disease of the newborn. Kiss [20] recently confirmed ABCB6 as a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from re- Figure 2. 3D structure models of ABCB6 in inward conformation.…”

Section: Discussionmentioning

confidence: 91%

“…The previous results demonstrated that ABCB6 is expressed in RBCs and during erythroid differentiation of K562 cells [20,21]. We examined ABCB6 expression and localization in an ex vivo model of erythroid differentiation.…”

Section: Abcb6 Expression During Erythroid Differentiationmentioning

confidence: 95%

“…We selected ABCB6 as a candidate gene based on its elevated expression in blood and bone marrow and its increased expression during erythroid differentiation (data not shown). The encoded ABCB6 protein is involved in porphyrin transport [19] and was recently identified in the RBC membrane [20].…”

Section: Evaluation Of Fp Critical Region Candidate Genesmentioning

confidence: 99%

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

Section: Introductionmentioning

confidence: 98%

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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: Discussionmentioning

confidence: 91%

Section: Abcb6 Expression During Erythroid Differentiationmentioning

confidence: 95%

Section: Evaluation Of Fp Critical Region Candidate Genesmentioning

confidence: 99%

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

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

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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An inventory of lysosomal ABC transporters

Abele

2020

FEBS Letters

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ABC transporters fulfill diverse physiological functions in different cellular localizations ranging from the plasma membrane to intracellular membranous compartments. Several ABC transporters have been spotted in the endolysosomal system, which consists of endosomes, autophagosomes, lysosomes and lysosome-related organelles. In this review we present an overview of lysosomal ABC transporters including ABCA2, ABCA3, ABCA5, ABCB6, ABCB9 and ABCD4, discussing their trafficking routes, putative substrates, potential physiological functions and associated diseases. In addition, we offer a critical Accepted Article This article is protected by copyright. All rights reserved evaluation of the literature linking ABC transporters to lysosomal drug sequestration, examining pitfalls associated with in vitro models of drug resistance.

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Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

Cited by 84 publications

References 63 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

An inventory of lysosomal ABC transporters

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