An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters

Guiying Cui; Jeong Hong; Yu Wen Chung-Davidson; Daniel Infield; Xin Xu; Jindong Li; Luba Simhaev; Netaly Khazanov; Brandon Stauffer; Barry Imhoff; Kirsten Cottrill; J. Edwin Blalock; Weiming Li; Hanoch Senderowitz; Eric Sorscher; Nael A. McCarty; Amit Gaggar

doi:10.1016/j.devcel.2019.09.017

An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters

Guiying Cui, Jeong Hong, Yu Wen Chung-Davidson, Daniel Infield, Xin Xu, Jindong Li, Luba Simhaev, Netaly Khazanov, Brandon Stauffer, Barry Imhoff, Kirsten Cottrill, J. Edwin Blalock, Weiming Li, Hanoch Senderowitz, Eric Sorscher, Nael A. McCarty, Amit Gaggar

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Pages (from-to)	421-430.e3
Journal	Developmental Cell
Volume	51
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2019.09.017
State	Published - 18 Nov 2019

Bibliographical note

Funding Information:
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, and Drs. Z. Plyer and I. Thornell for helpful discussions. This research is supported by the Great Lakes Fishery Commission (W.L.), NIH (HL102371 [A.G.] and 5R01-DK056481-07 [N.M.]), CF Foundation (MCCART17G0 [N.M.] and SENDER13XX0 [H.S.]), American Heart Association (16SDG27040000 [X.X.]), BSF (grant number 2013391 [H.S.]), Veterans Administration Merit Review (1 I01 BX001756 [A.G.]), and the Ismail Moustafa Scholar Fund (A.G.). G.C. J.H. Y.-W.C.-D. D.I. X.X. J.L. L.S. N.K. B.S. B.I. and K.C. performed the experiments. J.E.B. W.L. H.S. E.S. N.M. and A.G. analyzed key data generated from experiments; N.M. and A.G. supervised the project. All authors contributed to writing the manuscript. The authors declare no competing interests.

Funding Information:
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, and Drs. Z. Plyer and I. Thornell for helpful discussions. This research is supported by the Great Lakes Fishery Commission (W.L.), NIH ( HL102371 [A.G.] and 5R01-DK056481-07 [N.M.]), CF Foundation ( MCCART17G0 [N.M.] and SENDER13XX0 [H.S.]), American Heart Association ( 16SDG27040000 [X.X.]), BSF (grant number 2013391 [H.S.]), Veterans Administration Merit Review ( 1 I01 BX001756 [A.G.]), and the Ismail Moustafa Scholar Fund (A.G.).

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

ABC transporters
CFTR
channel
lamprey
molecular evolution
phosphorylation
vertebrates

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.devcel.2019.09.017

Cite this

Cui, G., Hong, J., Chung-Davidson, Y. W., Infield, D., Xu, X., Li, J., Simhaev, L., Khazanov, N., Stauffer, B., Imhoff, B., Cottrill, K., Blalock, J. E., Li, W., Senderowitz, H., Sorscher, E., McCarty, N. A., & Gaggar, A. (2019). An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters. Developmental Cell, 51(4), 421-430.e3. https://doi.org/10.1016/j.devcel.2019.09.017

@article{650dc8094a494eecab5d97b4d93687d8,

title = "An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters",

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.",

keywords = "ABC transporters, CFTR, channel, lamprey, molecular evolution, phosphorylation, vertebrates",

author = "Guiying Cui and Jeong Hong and Chung-Davidson, {Yu Wen} and Daniel Infield and Xin Xu and Jindong Li and Luba Simhaev and Netaly Khazanov and Brandon Stauffer and Barry Imhoff and Kirsten Cottrill and Blalock, {J. Edwin} and Weiming Li and Hanoch Senderowitz and Eric Sorscher and McCarty, {Nael A.} and Amit Gaggar",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = nov,

day = "18",

doi = "10.1016/j.devcel.2019.09.017",

language = "אנגלית",

volume = "51",

pages = "421--430.e3",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "4",

}

Cui, G, Hong, J, Chung-Davidson, YW, Infield, D, Xu, X, Li, J, Simhaev, L, Khazanov, N, Stauffer, B, Imhoff, B, Cottrill, K, Blalock, JE, Li, W, Senderowitz, H, Sorscher, E, McCarty, NA & Gaggar, A 2019, 'An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters', Developmental Cell, vol. 51, no. 4, pp. 421-430.e3. https://doi.org/10.1016/j.devcel.2019.09.017

TY - JOUR

T1 - An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters

AU - Cui, Guiying

AU - Hong, Jeong

AU - Chung-Davidson, Yu Wen

AU - Infield, Daniel

AU - Xu, Xin

AU - Li, Jindong

AU - Simhaev, Luba

AU - Khazanov, Netaly

AU - Stauffer, Brandon

AU - Imhoff, Barry

AU - Cottrill, Kirsten

AU - Blalock, J. Edwin

AU - Li, Weiming

AU - Senderowitz, Hanoch

AU - Sorscher, Eric

AU - McCarty, Nael A.

AU - Gaggar, Amit

PY - 2019/11/18

Y1 - 2019/11/18

N2 - 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.

AB - 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.

KW - ABC transporters

KW - CFTR

KW - channel

KW - lamprey

KW - molecular evolution

KW - phosphorylation

KW - vertebrates

UR - http://www.scopus.com/inward/record.url?scp=85074761552&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2019.09.017

DO - 10.1016/j.devcel.2019.09.017

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 31679858

AN - SCOPUS:85074761552

SN - 1534-5807

VL - 51

SP - 421-430.e3

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -

An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this