|
|
Blood, 15 January 2008, Vol. 111, No. 2, pp. 924-931.
Prepublished online as a Blood First Edition Paper on October 15, 2007; DOI 10.1182/blood-2007-07-100677.
 Previous Article | Table of Contents | Next Article 
RED CELLS
Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis
Laura Silvestri1,
Alessia Pagani1, and
Clara Camaschella1
1 Vita-Salute San Raffaele University–Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele, Milan, Italy
The liver peptide hepcidin regulates iron absorption and recycling. Hemojuvelin (HJV) has a key role in hepcidin regulation, and its inactivation causes severe iron overload both in humans and in mice. Membrane HJV (m-HJV) acts as a coreceptor for bone morphogenetic proteins (BMPs), whereas soluble HJV (s-HJV) may down-regulate hepcidin in a competitive way interfering with BMP signaling. s-HJV is decreased by iron in vitro and increased by iron deficiency in vivo. However, the mechanisms regulating the 2 HJV isoforms remain unclear. Here we show that s-HJV originates from a furin cleavage at position 332–335. s-HJV is reduced in the cleavage mutant R335Q as well as in cells treated with a furin inhibitor, and increased in cells overexpressing exogenous furin, but not in cells overexpressing an inactive furin variant. Furin is up-regulated by iron deficiency and hypoxia in association with the stabilization of HIF-1 . Increased s-HJV in response to HIF-1 occurs during differentiation of murine muscle cells expressing endogenous Hjv. Our data are relevant to the mechanisms that relate iron metabolism to the hypoxic response. The release of s-HJV might be a tissue-specific mechanism, signaling the local iron requests of hypoxic skeletal muscles independently of the oxygen status of the liver.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Iolascon, L. De Falco, and C. Beaumont
Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis
Haematologica,
March 1, 2009;
94(3):
395 - 408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Maxson, C. A. Enns, and A.-S. Zhang
Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells
Blood,
February 19, 2009;
113(8):
1786 - 1793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-S. Zhang and C. A. Enns
Iron Homeostasis: Recently Identified Proteins Provide Insight into Novel Control Mechanisms
J. Biol. Chem.,
January 9, 2009;
284(2):
711 - 715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Browne and D. Reddan
Potential role of bone morphogenetic protein (BMP) signalling as a potential therapeutic target for modification of iron balance
Nephrol. Dial. Transplant.,
January 1, 2009;
24(1):
28 - 30.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Swinkels and J. F. M. Wetzels
Hepcidin: a new tool in the management of anaemia in patients with chronic kidney disease?
Nephrol. Dial. Transplant.,
May 21, 2008;
(2008)
gfn267v1.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kuns-Hashimoto, D. Kuninger, M. Nili, and P. Rotwein
Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin
Am J Physiol Cell Physiol,
April 1, 2008;
294(4):
C994 - C1003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
