title: Scara5 is a ferritin receptor mediating non-transferrin iron delivery.
abstract: Developing organs require iron for a myriad of functions, but embryos deleted of the major adult transport proteins, transferrin or its receptor transferrin receptor1 (TfR1(-/-)), still initiate organogenesis, suggesting that non-transferrin pathways are important. To examine these pathways, we developed chimeras composed of fluorescence-tagged TfR1(-/-) cells and untagged wild-type cells. In the kidney, TfR1(-/-) cells populated capsule and stroma, mesenchyme and nephron, but were underrepresented in ureteric bud tips. Consistently, TfR1 provided transferrin to the ureteric bud, but not to the capsule or the stroma. Instead of transferrin, we found that the capsule internalized ferritin. Since the capsule expressed a novel receptor called Scara5, we tested its role in ferritin uptake and found that Scara5 bound serum ferritin and then stimulated its endocytosis from the cell surface with consequent iron delivery. These data implicate cell type-specific mechanisms of iron traffic in organogenesis, which alternatively utilize transferrin or non-transferrin iron delivery pathways.
authors.affiliation: Renal Division, College of Physicans & Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Jau Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Neal
authors.initials: N
authors.lastname: Paragas
authors.forename: Renee M
authors.initials: RM
authors.lastname: Ned
authors.forename: Andong
authors.initials: A
authors.lastname: Qiu
authors.forename: Melanie
authors.initials: M
authors.lastname: Viltard
authors.forename: Thomas
authors.initials: T
authors.lastname: Leete
authors.forename: Ian R
authors.initials: IR
authors.lastname: Drexler
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.forename: Farah
authors.initials: F
authors.lastname: Mohammed
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Chyuan Sheng
authors.initials: CS
authors.lastname: Lin
authors.forename: Kai M
authors.initials: KM
authors.lastname: Schmidt-Ott
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Andrews
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barasch
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002678:Chimera / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D005293:Ferritins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
chemical_list: D033862:Iron-Binding Proteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; C511405:SCARA5 protein, mouse; D051117:Scavenger Receptors, Class A; C480029:Tfrc protein, mouse; D014168:Transferrin; C027293:ferritin receptor; D005293:Ferritins; D007501:Iron