dc.contributor.author | Yanatori, Izumi | |
dc.contributor.author | Richardson, Des R | |
dc.contributor.author | Dhekne, Herschel S | |
dc.contributor.author | Toyokuni, Shinya | |
dc.contributor.author | Kishi, Fumio | |
dc.date.accessioned | 2021-11-03T22:47:25Z | |
dc.date.available | 2021-11-03T22:47:25Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.doi | 10.1182/blood.2021010995 | |
dc.identifier.uri | http://hdl.handle.net/10072/409747 | |
dc.description.abstract | Extracellular 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.peerreviewed | Yes | |
dc.language | eng | |
dc.publisher | American Society of Hematology | |
dc.relation.ispartofpagefrom | 1490 | |
dc.relation.ispartofpageto | 1503 | |
dc.relation.ispartofissue | 16 | |
dc.relation.ispartofjournal | Blood | |
dc.relation.ispartofvolume | 138 | |
dc.subject.fieldofresearch | Paediatrics | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearch | Haematology | |
dc.subject.fieldofresearchcode | 3213 | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.fieldofresearchcode | 320102 | |
dc.title | CD63 is regulated by iron via the IRE-IRP system and is important for ferritin secretion by extracellular vesicles | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Yanatori, 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.dateAccepted | 2021-06-24 | |
dc.date.updated | 2021-11-03T22:18:28Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Richardson, Des R. | |