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

Autor:	Luscieti S; Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute, Campus Can Ruti, Badalona, Spain.; Iron Metabolism: Regulation and Diseases Group, Josep Carreras Leukaemia Research Institute, Campus ICO-Germans Trias i Pujol, Badalona, Spain., Galy B; Division of Virus-Associated Carcinogenesis, German Cancer Research Centre, Heidelberg, Germany., Gutierrez L; Department of Biomaterials and Bioinspired Materials, Instituto de Ciencia de Materiales de Madrid, Madrid, Spain., Reinke M; Institute of Genetics, University of Bonn, Bonn, Germany., Couso J; Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute, Campus Can Ruti, Badalona, Spain.; Iron Metabolism: Regulation and Diseases Group, Josep Carreras Leukaemia Research Institute, Campus ICO-Germans Trias i Pujol, Badalona, Spain., Shvartsman M; Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute, Campus Can Ruti, Badalona, Spain., Di Pascale A; Department of Pharmacy, University of Naples Federico II, Naples, Italy; and., Witke W; Institute of Genetics, University of Bonn, Bonn, Germany., Hentze MW; European Molecular Biology Laboratory, Heidelberg, Germany., Pilo Boyl P; Institute of Genetics, University of Bonn, Bonn, Germany., Sanchez M; Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute, Campus Can Ruti, Badalona, Spain.; Iron Metabolism: Regulation and Diseases Group, Josep Carreras Leukaemia Research Institute, Campus ICO-Germans Trias i Pujol, Badalona, Spain.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2017 Oct 26; Vol. 130 (17), pp. 1934-1945. Date of Electronic Publication: 2017 Aug 03.
DOI:	10.1182/blood-2016-11-754382
Abstrakt:	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. (© 2017 by The American Society of Hematology.)
Databáze:	MEDLINE
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