Kinetics and Specificity of Feline Leukemia Virus Subgroup C Receptor (FLVCR) Export Function and Its Dependence on Hemopexin
| Autor: | Claudio Tiribelli, Raymond T. Doty, Zhantao Yang, Ann Smith, John D. Philips, Janis L. Abkowitz, J. Donald Ostrow, Pablo J. Giraudi |
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| Přispěvatelé: | Z., Yang, J. D., Philip, R. T., Doty, P., Giraudi, J. D., Ostrow, Tiribelli, Claudio, A., Smith, J. L., Abkowitz |
| Rok vydání: | 2010 |
| Předmět: |
genetics/metabolism
Hemorrhage genetics/metabolism Protoporphyrins Biochemistry genetics Humans Iron genetics/metabolism Homeostasi chemistry.chemical_compound Hemopexin Receptors Homeostasis genetics Heme chemistry.chemical_classification biology Protoporphyrin IX Membrane transport protein Viru Transferrin metabolism Membrane Transport Protein genetics Hemopexin Virus genetics/metabolism Transferrin Liver Receptors Virus metabolism Liver Rabbits Animals Biological Transport genetics Cell Line Coproporphyrins genetics/metabolism Heme genetics/metabolism Hemolysis genetics/metabolism Homeostasis metabolism Macrophages metabolism Membrane Transport Proteins genetics/metabolism Protoporphyrins genetics/metabolism Rabbits Rats Receptors genetics Cell Line Coproporphyrin Coproporphyrins Iron genetics/metabolism Rabbits Rats Receptor Hemorrhage Hemolysis Cell Line Animals Humans Heme export Molecular Biology Macrophages Membrane Transport Proteins Biological Transport Cell Biology genetics/metabolism Hemolysi Major facilitator superfamily Rats chemistry genetics/metabolism Protoporphyrin biology.protein Protoporphyrin metabolism Macrophage metabolism |
| Zdroj: | Journal of Biological Chemistry. 285:28874-28882 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.119131 |
| Popis: | The feline leukemia virus subgroup C receptor (FLVCR) is a heme export protein that is required for proerythroblast survival and facilitates macrophage heme iron recycling. However, its mechanism of heme export and substrate specificity are uncharacterized. Using [(55)Fe]heme and the fluorescent heme analog zinc mesoporphyrin, we investigated whether export by FLVCR depends on the availability and avidity of extracellular heme-binding proteins. Export was 100-fold more efficient when the medium contained hemopexin (K(d) < 1 pm) compared with albumin (K(d) = 5 nm) at the same concentration and was not detectable when the medium lacked heme-binding proteins. Besides heme, FLVCR could export other cyclic planar porphyrins, such as protoporphyrin IX and coproporphyrin. However, FLVCR has a narrow substrate range because unconjugated bilirubin, the primary breakdown product of heme, was not transported. As neither protoporphyrin IX nor coproporphyrin export improved with extracellular hemopexin (versus albumin), our observations further suggest that hemopexin, an abundant protein with a serum concentration (6.7-25 mum) equivalent to that of the iron transport protein transferrin (22-31 mum), by accepting heme from FLVCR and targeting it to the liver, might regulate macrophage heme export and heme iron recycling in vivo. Final studies show that hemopexin directly interacts with FLVCR, which also helps explain why FLVCR, in contrast to some major facilitator superfamily members, does not function as a bidirectional gradient-dependent transporter. Together, these data argue that hemopexin has a role in assuring systemic iron balance during homeostasis in addition to its established role as a scavenger during internal bleeding or hemolysis. |
| Databáze: | OpenAIRE |
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