An Intercellular Heme-Trafficking Protein Delivers Maternal Heme to the Embryo during Development in C. elegans

Department of Animal & Avian Sciences and Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Cell (Impact Factor: 32.24). 05/2011; 145(5):720-31. DOI: 10.1016/j.cell.2011.04.025
Source: PubMed


Extracellular free heme can intercalate into membranes and promote damage to cellular macromolecules. Thus it is likely that specific intercellular pathways exist for the directed transport, trafficking, and delivery of heme to cellular destinations, although none have been found to date. Here we show that Caenorhabditis elegans HRG-3 is required for the delivery of maternal heme to developing embryos. HRG-3 binds heme and is exclusively secreted by maternal intestinal cells into the interstitial fluid for transport of heme to extraintestinal cells, including oocytes. HRG-3 deficiency results either in death during embryogenesis or in developmental arrest immediately post-hatching-phenotypes that are fully suppressed by maternal but not zygotic hrg-3 expression. Our results establish a role for HRG-3 as an intercellular heme-trafficking protein.

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Available from: Iqbal Hamza, Jan 21, 2014
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    • "It is likely that homeostatic adaptation is controlled at the systemic level by bidirectional signaling between the intestine and extraintestinal tissues 484 Biometals (2015) 28:481–489 critically low heme conditions to ensure that oocytes developing within the germline receive the heme required for embryogenesis and larval development (Chen et al. 2011). This is accomplished by upregulation of HRG-3, an *8 kDa protein that is expressed in the intestine and binds to heme in a 2:1 (protein:heme) stoichiometric ratio (Fig. 2) (Chen et al. 2011). Although hrg-3 expression is upregulated more than 900 fold during heme deficiency, it is barely detectable when worms are grown in the presence of 6 lM heme. "
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    • "Mature HRG-3 is secreted into the worm's circulation and taken up by extracellular tissues and developing oocytes. When hrg-3 null worms are grown under heme limiting conditions, they show embryonic lethality and delayed growth, indicating a role for hrg-3 in the distribution of heme from the intestine during early embryonic and larval development (Chen et al., 2011). "
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