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Robey RW, Robinson AN, Ali-Rahmani F, et al. Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter. Sci Rep. 2021;11(1):24150doi: 10.1038/s41598-021-03500-8.
Robey, R. W., Robinson, A. N., Ali-Rahmani, F., Huff, L. M., Lusvarghi, S., Vahedi, S., Hotz, J. M., Warner, A. C., Butcher, D., Matta, J., Edmondson, E. F., Lee, T. D., Roth, J. S., Lee, O. W., Shen, M., Tanner, K., Hall, M. D., Ambudkar, S. V., & Gottesman, M. M. (2021). Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter. Scientific reports, 11(1), 24150. https://doi.org/10.1038/s41598-021-03500-8
Robey, Robert W, et al. "Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter." Scientific reports vol. 11,1 (2021): 24150. doi: https://doi.org/10.1038/s41598-021-03500-8
Robey RW, Robinson AN, Ali-Rahmani F, Huff LM, Lusvarghi S, Vahedi S, Hotz JM, Warner AC, Butcher D, Matta J, Edmondson EF, Lee TD, Roth JS, Lee OW, Shen M, Tanner K, Hall MD, Ambudkar SV, Gottesman MM. Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter. Sci Rep. 2021 Dec 17;11(1):24150. doi: 10.1038/s41598-021-03500-8. PMID: 34921178; PMCID: PMC8683423.
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Sci Rep. 2021 Dec 17;11(1):24150. doi: 10.1038/s41598-021-03500-8.

Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter.

Scientific reports

Robert W Robey, Andrea N Robinson, Fatima Ali-Rahmani, Lyn M Huff, Sabrina Lusvarghi, Shahrooz Vahedi, Jordan M Hotz, Andrew C Warner, Donna Butcher, Jennifer Matta, Elijah F Edmondson, Tobie D Lee, Jacob S Roth, Olivia W Lee, Min Shen, Kandice Tanner, Matthew D Hall, Suresh V Ambudkar, Michael M Gottesman

Affiliations

  1. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  2. Molecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  3. National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
  4. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. [email protected].

PMID: 34921178 PMCID: PMC8683423 DOI: 10.1038/s41598-021-03500-8

Abstract

Capillary endothelial cells of the human blood-brain barrier (BBB) express high levels of P-glycoprotein (P-gp, encoded by ABCB1) and ABCG2 (encoded by ABCG2). However, little information is available regarding ATP-binding cassette transporters expressed at the zebrafish BBB, which has emerged as a potential model system. We report the characterization and tissue localization of two genes that are similar to ABCB1, zebrafish abcb4 and abcb5. When stably expressed in HEK293 cells, both Abcb4 and Abcb5 conferred resistance to P-gp substrates; however, Abcb5 poorly transported doxorubicin and mitoxantrone compared to zebrafish Abcb4. Additionally, Abcb5 did not transport the fluorescent P-gp probes BODIPY-ethylenediamine or LDS 751, while they were transported by Abcb4. High-throughput screening of 90 human P-gp substrates confirmed that Abcb4 has an overlapping substrate specificity profile with P-gp. In the brain vasculature, RNAscope probes for abcb4 colocalized with staining by the P-gp antibody C219, while abcb5 was not detected. The abcb4 probe also colocalized with claudin-5 in brain endothelial cells. Abcb4 and Abcb5 had different tissue localizations in multiple zebrafish tissues, potentially indicating different functions. The data suggest that zebrafish Abcb4 functionally phenocopies P-gp and that the zebrafish may serve as a model to study the role of P-gp at the BBB.

© 2021. The Author(s).

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