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dc.contributor.authorYanatori, Izumi
dc.contributor.authorRichardson, Des R
dc.contributor.authorDhekne, Herschel S
dc.contributor.authorToyokuni, Shinya
dc.contributor.authorKishi, Fumio
dc.date.accessioned2021-11-03T22:47:25Z
dc.date.available2021-11-03T22:47:25Z
dc.date.issued2021
dc.identifier.issn0006-4971
dc.identifier.doi10.1182/blood.2021010995
dc.identifier.urihttp://hdl.handle.net/10072/409747
dc.description.abstractExtracellular vesicles (EVs) transfer functional molecules between cells. CD63 is a widely recognized EV marker that contributes to EV secretion from cells. However, the regulation of its expression remains largely unknown. Ferritin is a cellular iron storage protein that can also be secreted by the exosome pathway, and serum ferritin levels classically reflect body iron stores. Iron metabolism-associated proteins such as ferritin are intricately regulated by cellular iron levels via the iron responsive element-iron regulatory protein (IRE-IRP) system. Herein, we present a novel mechanism demonstrating that the expression of the EV-associated protein CD63 is under the regulation of the IRE-IRP system. We discovered a canonical IRE in the 5' untranslated region of CD63 messenger RNA that is responsible for regulating its expression in response to increased iron. Cellular iron loading caused a marked increase in CD63 expression and the secretion of CD63+ EVs from cells, which were shown to contain ferritin-H and ferritin-L. Our results demonstrate that under iron loading, intracellular ferritin is transferred via nuclear receptor coactivator 4 (NCOA4) to CD63+ EVs that are then secreted. Such iron-regulated secretion of the major iron storage protein ferritin via CD63+ EVs, is significant for understanding the local cell-to-cell exchange of ferritin and iron.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherAmerican Society of Hematology
dc.relation.ispartofpagefrom1490
dc.relation.ispartofpageto1503
dc.relation.ispartofissue16
dc.relation.ispartofjournalBlood
dc.relation.ispartofvolume138
dc.subject.fieldofresearchPaediatrics
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchHaematology
dc.subject.fieldofresearchcode3213
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode320102
dc.titleCD63 is regulated by iron via the IRE-IRP system and is important for ferritin secretion by extracellular vesicles
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationYanatori, I; Richardson, DR; Dhekne, HS; Toyokuni, S; Kishi, F, CD63 is regulated by iron via the IRE-IRP system and is important for ferritin secretion by extracellular vesicles., Blood, 2021, 138 (16), pp. 1490-1503
dcterms.dateAccepted2021-06-24
dc.date.updated2021-11-03T22:18:28Z
gro.hasfulltextNo Full Text
gro.griffith.authorRichardson, Des R.


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