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

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 and Iqbal Hamza ()
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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

Nature, 2008, vol. 453, issue 7198, 1127-1131

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.

Date: 2008
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DOI: 10.1038/nature06934

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