Identification of a human heme exporter that is essential for erythropoiesis

John G. Quigley; Zhantao Yang; Mark T. Worthington; John D. Phillips; Kathleen M. Sabo; Daniel E. Sabath; Carl L. Berg; Shigeru Sassa; Brent L. Wood; Janis L. Abkowitz

doi:10.1016/j.cell.2004.08.014

Identification of a human heme exporter that is essential for erythropoiesis

John G. Quigley, Zhantao Yang, Mark T. Worthington, John D. Phillips, Kathleen M. Sabo, Daniel E. Sabath, Carl L. Berg, Shigeru Sassa, Brent L. Wood, Janis L. Abkowitz

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

287 Scopus citations

Abstract

FLVCR, a member of the major facilitator superfamily of transporter proteins, is the cell surface receptor for feline leukemia virus, subgroup C. Retroviral interference with FLVCR display results in a loss of erythroid progenitors (colony-forming units-erythroid, CFU-E) and severe anemia in cats. In this report, we demonstrate that human FLVCR exports cytoplasmic heme and hypothesize that human FLVCR is required on developing erythroid cells to protect them from heme toxicity. Inhibition of FLVCR in K562 cells decreases heme export, impairs their erythroid maturation and leads to apoptosis. FLVCR is upregulated on CFU-E, indicating that heme export is important in primary cells at this stage. Studies of FLVCR expression in cell lines suggest this exporter also impacts heme trafficking in intestine and liver. To our knowledge, this is the first description of a mammalian heme transporter.

Original language	English (US)
Pages (from-to)	757-766
Number of pages	10
Journal	Cell
Volume	118
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2004.08.014
State	Published - Sep 17 2004
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2004.08.014

Cite this

@article{88723f59dc5f4585bfeac7e9658981b2,

title = "Identification of a human heme exporter that is essential for erythropoiesis",

abstract = "FLVCR, a member of the major facilitator superfamily of transporter proteins, is the cell surface receptor for feline leukemia virus, subgroup C. Retroviral interference with FLVCR display results in a loss of erythroid progenitors (colony-forming units-erythroid, CFU-E) and severe anemia in cats. In this report, we demonstrate that human FLVCR exports cytoplasmic heme and hypothesize that human FLVCR is required on developing erythroid cells to protect them from heme toxicity. Inhibition of FLVCR in K562 cells decreases heme export, impairs their erythroid maturation and leads to apoptosis. FLVCR is upregulated on CFU-E, indicating that heme export is important in primary cells at this stage. Studies of FLVCR expression in cell lines suggest this exporter also impacts heme trafficking in intestine and liver. To our knowledge, this is the first description of a mammalian heme transporter.",

author = "Quigley, {John G.} and Zhantao Yang and Worthington, {Mark T.} and Phillips, {John D.} and Sabo, {Kathleen M.} and Sabath, {Daniel E.} and Berg, {Carl L.} and Shigeru Sassa and Wood, {Brent L.} and Abkowitz, {Janis L.}",

note = "Funding Information: We thank R.T. Doty and H.A. Dailey for critical reading of the manuscript. This work was supported by grants from the NIH to J.L.A. (HL31823), S.S. (DK32890), and J.D.P. (DK20503) and the Center for Clinical Research at the University of Washington (RR00037).",

year = "2004",

month = sep,

day = "17",

doi = "10.1016/j.cell.2004.08.014",

language = "English (US)",

volume = "118",

pages = "757--766",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Identification of a human heme exporter that is essential for erythropoiesis

AU - Quigley, John G.

AU - Yang, Zhantao

AU - Worthington, Mark T.

AU - Phillips, John D.

AU - Sabo, Kathleen M.

AU - Sabath, Daniel E.

AU - Berg, Carl L.

AU - Sassa, Shigeru

AU - Wood, Brent L.

AU - Abkowitz, Janis L.

N1 - Funding Information: We thank R.T. Doty and H.A. Dailey for critical reading of the manuscript. This work was supported by grants from the NIH to J.L.A. (HL31823), S.S. (DK32890), and J.D.P. (DK20503) and the Center for Clinical Research at the University of Washington (RR00037).

PY - 2004/9/17

Y1 - 2004/9/17

N2 - FLVCR, a member of the major facilitator superfamily of transporter proteins, is the cell surface receptor for feline leukemia virus, subgroup C. Retroviral interference with FLVCR display results in a loss of erythroid progenitors (colony-forming units-erythroid, CFU-E) and severe anemia in cats. In this report, we demonstrate that human FLVCR exports cytoplasmic heme and hypothesize that human FLVCR is required on developing erythroid cells to protect them from heme toxicity. Inhibition of FLVCR in K562 cells decreases heme export, impairs their erythroid maturation and leads to apoptosis. FLVCR is upregulated on CFU-E, indicating that heme export is important in primary cells at this stage. Studies of FLVCR expression in cell lines suggest this exporter also impacts heme trafficking in intestine and liver. To our knowledge, this is the first description of a mammalian heme transporter.

AB - FLVCR, a member of the major facilitator superfamily of transporter proteins, is the cell surface receptor for feline leukemia virus, subgroup C. Retroviral interference with FLVCR display results in a loss of erythroid progenitors (colony-forming units-erythroid, CFU-E) and severe anemia in cats. In this report, we demonstrate that human FLVCR exports cytoplasmic heme and hypothesize that human FLVCR is required on developing erythroid cells to protect them from heme toxicity. Inhibition of FLVCR in K562 cells decreases heme export, impairs their erythroid maturation and leads to apoptosis. FLVCR is upregulated on CFU-E, indicating that heme export is important in primary cells at this stage. Studies of FLVCR expression in cell lines suggest this exporter also impacts heme trafficking in intestine and liver. To our knowledge, this is the first description of a mammalian heme transporter.

UR - http://www.scopus.com/inward/record.url?scp=4544264523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544264523&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2004.08.014

DO - 10.1016/j.cell.2004.08.014

M3 - Article

C2 - 15369674

AN - SCOPUS:4544264523

SN - 0092-8674

VL - 118

SP - 757

EP - 766

JO - Cell

JF - Cell

IS - 6

ER -

Identification of a human heme exporter that is essential for erythropoiesis

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this