TY - JOUR
T1 - Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells
AU - Maxson, Julia E.
AU - Enns, Caroline A.
AU - Zhang, An Sheng
PY - 2009/2/19
Y1 - 2009/2/19
N2 - Hemojuvelin (HJV) was recently identified as a critical regulator of iron ho-meostasis. It is either associated with cell membranes through a glycosylphosphati-dylinositol anchor or released as a soluble form. Membrane-anchored HJV acts as a coreceptor for bone morphogenetic proteins and activates the transcription of hepcidin, a hormone that regulates iron efflux from cells. Soluble HJV antagonizes bone morphogenetic protein signaling and suppresses hepcidin expression. In this study, we examined the trafficking and processing of HJV. Cellular HJV reached the plasma membrane without obtaining complex oligosaccharides, indicating that HJV avoided Golgi processing. Secreted HJV, in contrast, has complex oligosaccharides and can be derived from HJV with high-mannose oligosac-charides at the plasma membrane. Our results support a model in which retrograde trafficking of HJV before cleavage is the predominant processing pathway. Release of HJV requires it to bind to the transmembrane receptor neogenin. Neo-genin does not, however, play a role in HJV trafficking to the cell surface, suggesting that it could be involved either in retrograde trafficking of HJV or in cleavage leading to HJV release.
AB - Hemojuvelin (HJV) was recently identified as a critical regulator of iron ho-meostasis. It is either associated with cell membranes through a glycosylphosphati-dylinositol anchor or released as a soluble form. Membrane-anchored HJV acts as a coreceptor for bone morphogenetic proteins and activates the transcription of hepcidin, a hormone that regulates iron efflux from cells. Soluble HJV antagonizes bone morphogenetic protein signaling and suppresses hepcidin expression. In this study, we examined the trafficking and processing of HJV. Cellular HJV reached the plasma membrane without obtaining complex oligosaccharides, indicating that HJV avoided Golgi processing. Secreted HJV, in contrast, has complex oligosaccharides and can be derived from HJV with high-mannose oligosac-charides at the plasma membrane. Our results support a model in which retrograde trafficking of HJV before cleavage is the predominant processing pathway. Release of HJV requires it to bind to the transmembrane receptor neogenin. Neo-genin does not, however, play a role in HJV trafficking to the cell surface, suggesting that it could be involved either in retrograde trafficking of HJV or in cleavage leading to HJV release.
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U2 - 10.1182/blood-2008-08-174565
DO - 10.1182/blood-2008-08-174565
M3 - Article
C2 - 19029439
AN - SCOPUS:61849129278
SN - 0006-4971
VL - 113
SP - 1786
EP - 1793
JO - Blood
JF - Blood
IS - 8
ER -