The actin binding protein profilin 2 is a novel regulator of iron homeostasis

Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 (Pfn2) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter re...

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Detalles Bibliográficos
Autores: Luscieti, Sara, Galy, Bruno, Gutierrez, Lucia, Reinke, Michael, Couso, Jorge, Shvartsman, Maya, Di Pascale, Antonio, Witke, Walter, Hentze, Matthias W., Pilo Boyl, Pietro, Sanchez, Mayka
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:20.500.12328/3939
Acceso en línea:http://hdl.handle.net/20.500.12328/3939
https://dx.doi.org/10.1182/blood-2016-11-754382
Access Level:acceso abierto
Palabra clave:Glòbuls vermells
Ferro
Eritropoesi
Glóbulos rojos
Hierro
Eritropoyesis
Red cells
Iron
Erythropoiesis
61
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spelling The actin binding protein profilin 2 is a novel regulator of iron homeostasisLuscieti, SaraGaly, BrunoGutierrez, LuciaReinke, MichaelCouso, JorgeShvartsman, MayaDi Pascale, AntonioWitke, WalterHentze, Matthias W.Pilo Boyl, PietroSanchez, MaykaGlòbuls vermellsFerroEritropoesiGlóbulos rojosHierroEritropoyesisRed cellsIronErythropoiesis61Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 (Pfn2) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter release, as a novel IRP-interacting transcript, and studied its role in iron metabolism. A combination of electrophoretic mobility shift assay experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3′ untranslated region of Pfn2 mRNA. Pfn2 mRNA levels were significantly reduced in duodenal samples from mice with intestinal IRP ablation, suggesting that IRPs exert a positive effect on Pfn2 mRNA expression in vivo. Overexpression of Pfn2 in HeLa and Hepa1-6 cells reduced their metabolically active iron pool. Importantly, Pfn2-deficient mice showed iron accumulation in discrete areas of the brain (olfactory bulb, hippocampus, and midbrain) and reduction of the hepatic iron store without anemia. Despite low liver iron levels, hepatic hepcidin expression remained high, likely because of compensatory activation of hepcidin by mild inflammation. Splenic ferroportin was increased probably to sustain hematopoiesis. Overall, our results indicate that Pfn2 expression is controlled by the IRPs in vivo and that Pfn2 contributes to maintaining iron homeostasis in cell lines and mice.info:eu-repo/semantics/publishedVersionASH Publication2017info:eu-repo/semantics/article12http://hdl.handle.net/20.500.12328/3939https://dx.doi.org/10.1182/blood-2016-11-754382reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBlood130;17info:eu-repo/semantics/openAccessoai:recercat.cat:20.500.12328/39392026-05-29T05:05:01Z
dc.title.none.fl_str_mv The actin binding protein profilin 2 is a novel regulator of iron homeostasis
title The actin binding protein profilin 2 is a novel regulator of iron homeostasis
spellingShingle The actin binding protein profilin 2 is a novel regulator of iron homeostasis
Luscieti, Sara
Glòbuls vermells
Ferro
Eritropoesi
Glóbulos rojos
Hierro
Eritropoyesis
Red cells
Iron
Erythropoiesis
61
title_short The actin binding protein profilin 2 is a novel regulator of iron homeostasis
title_full The actin binding protein profilin 2 is a novel regulator of iron homeostasis
title_fullStr The actin binding protein profilin 2 is a novel regulator of iron homeostasis
title_full_unstemmed The actin binding protein profilin 2 is a novel regulator of iron homeostasis
title_sort The actin binding protein profilin 2 is a novel regulator of iron homeostasis
dc.creator.none.fl_str_mv Luscieti, Sara
Galy, Bruno
Gutierrez, Lucia
Reinke, Michael
Couso, Jorge
Shvartsman, Maya
Di Pascale, Antonio
Witke, Walter
Hentze, Matthias W.
Pilo Boyl, Pietro
Sanchez, Mayka
author Luscieti, Sara
author_facet Luscieti, Sara
Galy, Bruno
Gutierrez, Lucia
Reinke, Michael
Couso, Jorge
Shvartsman, Maya
Di Pascale, Antonio
Witke, Walter
Hentze, Matthias W.
Pilo Boyl, Pietro
Sanchez, Mayka
author_role author
author2 Galy, Bruno
Gutierrez, Lucia
Reinke, Michael
Couso, Jorge
Shvartsman, Maya
Di Pascale, Antonio
Witke, Walter
Hentze, Matthias W.
Pilo Boyl, Pietro
Sanchez, Mayka
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glòbuls vermells
Ferro
Eritropoesi
Glóbulos rojos
Hierro
Eritropoyesis
Red cells
Iron
Erythropoiesis
61
topic Glòbuls vermells
Ferro
Eritropoesi
Glóbulos rojos
Hierro
Eritropoyesis
Red cells
Iron
Erythropoiesis
61
description Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 (Pfn2) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter release, as a novel IRP-interacting transcript, and studied its role in iron metabolism. A combination of electrophoretic mobility shift assay experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3′ untranslated region of Pfn2 mRNA. Pfn2 mRNA levels were significantly reduced in duodenal samples from mice with intestinal IRP ablation, suggesting that IRPs exert a positive effect on Pfn2 mRNA expression in vivo. Overexpression of Pfn2 in HeLa and Hepa1-6 cells reduced their metabolically active iron pool. Importantly, Pfn2-deficient mice showed iron accumulation in discrete areas of the brain (olfactory bulb, hippocampus, and midbrain) and reduction of the hepatic iron store without anemia. Despite low liver iron levels, hepatic hepcidin expression remained high, likely because of compensatory activation of hepcidin by mild inflammation. Splenic ferroportin was increased probably to sustain hematopoiesis. Overall, our results indicate that Pfn2 expression is controlled by the IRPs in vivo and that Pfn2 contributes to maintaining iron homeostasis in cell lines and mice.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12328/3939
https://dx.doi.org/10.1182/blood-2016-11-754382
url http://hdl.handle.net/20.500.12328/3939
https://dx.doi.org/10.1182/blood-2016-11-754382
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Blood
130;17
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12
dc.publisher.none.fl_str_mv ASH Publication
publisher.none.fl_str_mv ASH Publication
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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