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Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins

Author

Listed:
  • Abbhirami Rajagopal

    (University of Maryland, College Park, Maryland 20742, USA)

  • Anita U. Rao

    (University of Maryland, College Park, Maryland 20742, USA)

  • Julio Amigo

    (Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Meng Tian

    (Children’s Hospital Boston, Boston, Massachusetts 02115, USA)

  • Sanjeev K. Upadhyay

    (National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK campus)

  • Caitlin Hall

    (University of Maryland, College Park, Maryland 20742, USA)

  • Suji Uhm

    (University of Maryland, College Park, Maryland 20742, USA)

  • M. K. Mathew

    (National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK campus)

  • Mark D. Fleming

    (Children’s Hospital Boston, Boston, Massachusetts 02115, USA)

  • Barry H. Paw

    (Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Michael Krause

    (Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Iqbal Hamza

    (University of Maryland, College Park, Maryland 20742, USA)

Abstract

Haem homeostasis: Role of HRG-1 proteins The three-dimensional structures of haemoglobin and scores of other haem-containing proteins have been determined and the biosynthesis of haem has been thoroughly studied. But little is known about what happens to haems within the cell. The roundworm C. elegans can help fill this gap: it is a haem auxotroph, which means that although it needs haem for its haemoproteins, it can't synthesize it so scavenges its supplies from its surroundings. Exploiting the worm's well defined genetics and with no endogenous haem to complicate matters, Rajagopal et al. identified HRG-1 and HRG-4, previously unknown transmembrane proteins, as essential to haem utilization. These proteins are broadly conserved in animals and in humans: for instance, zebrafish with lowered levels of HRG-1 show anaemia, and severe depletion of HRG-1 causes congenital malformations as other haem proteins crucial for development are also affected. The discovery of this haem transport mechanism may provide insights into human disorders — as well as possible drug targets for new anthelmintics to fight worm infestations.

Suggested Citation

  • Abbhirami Rajagopal & Anita U. Rao & Julio Amigo & Meng Tian & Sanjeev K. Upadhyay & Caitlin Hall & Suji Uhm & M. K. Mathew & Mark D. Fleming & Barry H. Paw & Michael Krause & Iqbal Hamza, 2008. "Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins," Nature, Nature, vol. 453(7198), pages 1127-1131, June.
    • Handle: RePEc:nat:nature:v:453:y:2008:i:7198:d:10.1038_nature06934
    DOI: 10.1038/nature06934
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