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Special Issue "Physiological and Pathological Roles of ABC Transporters 2.0"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 August 2020.

Special Issue Editors

Dr. Markus Frank
Website
Guest Editor
1. Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
2. Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
3. School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
Special Issues and Collections in MDPI journals
Dr. Natasha Frank
Website
Guest Editor
Assistant Professor of Medicine, Harvard Medical School, Boston, MA, USA; Director, VA Boston Genetic Service; Division of Genetics, Brigham and Women’s Hospital, Boston, MA, USA

Special Issue Information

Dear colleagues,

This Special Issue is the continuation of our previous special issue " Physiological and Pathological Roles of ABC Transporters".

The human ATP-Binding Cassette (ABC) superfamily of molecules contains members with broad relevance to multiple physiological functions, which are associated with significant distinct disease states when mutated or dysregulated, while at the same time representing, in such situations, promising emerging targets for therapeutic interventions. The overarching goal of this ABC Molecule Thematic Issue is to present (i) a state-of-the-art overview of the structure and function of ABC proteins; (ii) to present examples of ABC-associated genetic disorders that have already been successfully targeted or represent emerging targets for molecular therapeutic intervention; (iii) to review important recent advances in the roles of ABC molecules in stem cell biology and explore how this knowledge can be transformed to clinical applications in novel stem cell-based tissue-regenerative or anti-cancer approaches; and (iv) to present the latest findings on the roles of ABC members as drug resistance mediators and potential targets in pharmacological cancer therapy. While a comprehensive treatment of all the broad and important advances of the ABC field can obviously not be offered in a single thematic issue, we nevertheless strive to present important examples of some particularly dynamic and stimulating aspects of this exciting field.

Dr. Markus Frank
Dr. Natasha Frank
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ATP-binding cassette, ABC transporters
  • structure, function
  • CFTR, ABCA4, ABCB1, ABCB5, ABCG2
  • stem cells, cancer stem cells
  • tissue regeneration
  • cancer therapy
  • drug resistance
  • cystic fibrosis
  • Stargardt’s Disease
  • Limbal Stem Cell Deficiency

Related Special Issue

Published Papers (3 papers)

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Research

Open AccessArticle
Characterization of ABC Transporters in EpiAirway™, a Cellular Model of Normal Human Bronchial Epithelium
Int. J. Mol. Sci. 2020, 21(9), 3190; https://doi.org/10.3390/ijms21093190 - 30 Apr 2020
Cited by 1
Abstract
The ATP-binding cassette (ABC) transporters P-glycoprotein (MDR1/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) play a crucial role in the translocation of a broad range of drugs; data about their expression and activity [...] Read more.
The ATP-binding cassette (ABC) transporters P-glycoprotein (MDR1/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) play a crucial role in the translocation of a broad range of drugs; data about their expression and activity in lung tissue are controversial. Here, we address their expression, localization and function in EpiAirway™, a three-dimensional (3D)-model of human airways; Calu-3 cells, a representative in vitro model of bronchial epithelium, are used for comparison. Transporter expression has been evaluated with RT-qPCR and Western blot, the localization with immunocytochemistry, and the activity by measuring the apical-to-basolateral and basolateral-to-apical fluxes of specific substrates in the presence of inhibitors. EpiAirway™ and Calu-3 cells express high levels of MRP1 on the basolateral membrane, while they profoundly differ in terms of BCRP and MDR1: BCRP is detected in EpiAirway™, but not in Calu-3 cells, while MDR1 is expressed and functional only in fully-differentiated Calu-3; in EpiAirway™, MDR1 expression and activity are undetectable, consistently with the absence of the protein in specimens from human healthy bronchi. In summary, EpiAirway™ appears to be a promising tool to study the mechanisms of drug delivery in the bronchial epithelium and to clarify the role of ABC transporters in the modulation of the bioavailability of administered drugs. Full article
(This article belongs to the Special Issue Physiological and Pathological Roles of ABC Transporters 2.0)
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Open AccessArticle
ATP Binding Cassette Transporter A1 is Involved in Extracellular Secretion of Acetylated APE1/Ref-1
Int. J. Mol. Sci. 2019, 20(13), 3178; https://doi.org/10.3390/ijms20133178 - 28 Jun 2019
Cited by 2
Abstract
Acetylation of nuclear apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is associated with its extracellular secretion, despite the lack of an N-terminal protein secretion signal. In this study, we investigated plasma membrane targeting and translocation of APE1/Ref-1 in HEK293T cells with enhanced acetylation. While APE1/Ref-1 targeting [...] Read more.
Acetylation of nuclear apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is associated with its extracellular secretion, despite the lack of an N-terminal protein secretion signal. In this study, we investigated plasma membrane targeting and translocation of APE1/Ref-1 in HEK293T cells with enhanced acetylation. While APE1/Ref-1 targeting was not affected by inhibition of the endoplasmic reticulum/Golgi-dependent secretion, its secretion was reduced by inhibitors of ATP-binding cassette (ABC) transporters, and siRNA-mediated down-regulation of ABC transporter A1. The association between APE1/Ref-1 and ABCA1 transporter was confirmed by proximal ligation assay and immunoprecipitation experiments. An APE1/Ref-1 construct with mutated acetylation sites (K6/K7R) showed reduced co-localization with ABC transporter A1. Exposure of trichostatin A (TSA) induced the acetylation of APE1/Ref-1, which translocated into membrane fraction. Taken together, acetylation of APE1/Ref-1 is considered to be necessary for its extracellular targeting via non-classical secretory pathway using the ABCA1 transporter. Full article
(This article belongs to the Special Issue Physiological and Pathological Roles of ABC Transporters 2.0)
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Open AccessArticle
Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort
Int. J. Mol. Sci. 2018, 19(8), 2196; https://doi.org/10.3390/ijms19082196 - 27 Jul 2018
Cited by 6
Abstract
Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and [...] Read more.
Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and direct Sanger sequencing. At the end of the screening, at least two likely pathogenic mutations were found in 302 patients (76.1%) while 95 remained unsolved: 40 (10.1%) with no variants identified, 52 (13.1%) with one heterozygous mutation, and 3 (0.7%) with at least one variant of uncertain significance (VUS). Sixty-three novel variants were identified in the cohort. Three of them were variants of uncertain significance. The other 60 mutations were classified as likely pathogenic or pathogenic, and were identified in 61 patients (15.4%). The majority of those were missense (55%) followed by frameshift and nonsense (30%), intronic (11.7%) variants, and in-frame deletions (3.3%). Only patients with variants never reported in literature were further analyzed herein. Recruited subjects underwent complete ophthalmic examination including best corrected visual acuity, kinetic and static perimetry, color vision test, full-field and multifocal electroretinography, color fundus photography, short-wavelength and near-infrared fundus autofluorescence imaging, and spectral domain optical coherence tomography. Clinical evaluation of each subject confirms the tendency that truncating mutations lead to a more severe phenotype with electroretinogram (ERG) impairment (p = 0.002) and an earlier age of onset (p = 0.037). Our study further expands the mutation spectrum in the exonic and flanking regions of ABCA4 underlying Stargardt disease. Full article
(This article belongs to the Special Issue Physiological and Pathological Roles of ABC Transporters 2.0)
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