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Author Notes:

Amit Gaggar MD PhD, 845 19th Street South, Room 812, University of Alabama at Birmingham, Birmingham, AL 35294, Phone: 205-934-6439, agaggar@uabmc.edu

Author contributions: GC, JH, YC-D, DI, XX, JL, LS, NK, BS, BI, KC performed the experiments. JEB, WL, HS, ES, NM, and AG analyzed key data generated from experiments; NM and AG supervised the project. All authors contributed to writing the manuscript.

We would like to thank Dr. Dezhi Wang at UAB Pathology Core Research Laboratory for help in histology, Drs. K. Kirk and J. Koff for their careful examination of this manuscript, Drs. Z. Plyer and I. Thornell for helpful discussions.

The authors declare no competing interests.

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Research Funding:

This research is supported by the Great Lakes Fishery Commission (WL), NIH (HL102371 (AG), 5R01-DK056481-07 (NM)), CF Foundation (MCCART17G0 (NM) and SENDER13XX0 (HS)), American Heart Association (16SDG27040000 (XX)), BSF (Grant number 2013391 (HS)), Veterans Administration Merit Review (1 I01 BX001756 (AG)), and the Ismail Moustafa Scholar Fund (AG).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • Developmental Biology
  • TRANSMEMBRANE CONDUCTANCE REGULATOR
  • EXTRACELLULAR LOOP 1
  • PORE ARCHITECTURE
  • IDENTIFICATION
  • LOCALIZATION
  • MURINE
  • CAMP

An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters

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Journal Title:

DEVELOPMENTAL CELL

Volume:

Volume 51, Number 4

Publisher:

, Pages 421-+

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development of secretory diarrhea and cystic fibrosis. The oldest CFTR ortholog identified is from dogfish shark, which retains similar structural and functional characteristics to the mammalian protein, thereby highlighting CFTR's critical role in regulating epithelial ion transport in vertebrates. However, the identification of an early CFTR ortholog with altered structure or function would provide critical insight into the evolution of epithelial anion transport. Here, we describe the earliest known CFTR, expressed in sea lamprey (Petromyzon marinus), with unique structural features, altered kinetics of activation and sensitivity to inhibition, and altered single-channel conductance compared to human CFTR. Our data provide the earliest evolutionary evidence of CFTR, offering insight regarding changes in gene and protein structure that underpin evolution from transporter to anion channel. Importantly, these data provide a unique platform to enhance our understanding of vertebrate phylogeny over a critical period of evolutionary expansion.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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