000075695 001__ 75695
000075695 005__ 20190709135653.0
000075695 0247_ $$2doi$$a10.1182/blood-2016-11-754382
000075695 0248_ $$2sideral$$a105573
000075695 037__ $$aART-2017-105573
000075695 041__ $$aeng
000075695 100__ $$aLuscieti, S.
000075695 245__ $$aThe actin-binding protein profilin 2 is a novel regulator of iron homeostasis
000075695 260__ $$c2017
000075695 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075695 5203_ $$aCellular 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 39 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.
000075695 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2015-70412-R
000075695 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000075695 590__ $$a15.132$$b2017
000075695 591__ $$aHEMATOLOGY$$b2 / 71 = 0.028$$c2017$$dQ1$$eT1
000075695 592__ $$a6.434$$b2017
000075695 593__ $$aBiochemistry$$c2017$$dQ1
000075695 593__ $$aImmunology$$c2017$$dQ1
000075695 593__ $$aHematology$$c2017$$dQ1
000075695 593__ $$aCell Biology$$c2017$$dQ1
000075695 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000075695 700__ $$aGaly, B.
000075695 700__ $$0(orcid)0000-0003-2366-3598$$aGutierrez, L.$$uUniversidad de Zaragoza
000075695 700__ $$aReinke, M.
000075695 700__ $$aCouso, J.
000075695 700__ $$aShvartsman, M.
000075695 700__ $$aDi Pascale, A.
000075695 700__ $$aWitke, W.
000075695 700__ $$aHentze, M.W.
000075695 700__ $$aBoyl, P.P.
000075695 700__ $$aSanchez, M.
000075695 7102_ $$12009$$2750$$aUniversidad de Zaragoza$$bDpto. Química Analítica$$cÁrea Química Analítica
000075695 773__ $$g130, 17 (2017), 1934-1945$$pBlood$$tBLOOD$$x0006-4971
000075695 8564_ $$s1818988$$uhttps://zaguan.unizar.es/record/75695/files/texto_completo.pdf$$yPostprint
000075695 8564_ $$s68794$$uhttps://zaguan.unizar.es/record/75695/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000075695 909CO $$ooai:zaguan.unizar.es:75695$$particulos$$pdriver
000075695 951__ $$a2019-07-09-12:44:36
000075695 980__ $$aARTICLE