title: Snx3 regulates recycling of the transferrin receptor and iron assimilation.
abstract: Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors. Snx3 is highly expressed in vertebrate hematopoietic tissues. Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates due to impaired transferrin (Tf)-mediated iron uptake and its accumulation in early endosomes. This impaired iron assimilation can be complemented with non-Tf iron chelates. We show that Snx3 and Vps35, a component of the retromer, interact with Tfrc to sort it to the recycling endosomes. Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism.
authors: Department of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Caiyong
authors: C
authors: Chen
authors: Daniel
authors: D
authors: Garcia-Santos
authors: Yuichi
authors: Y
authors: Ishikawa
authors: Alexandra
authors: A
authors: Seguin
authors: Liangtao
authors: L
authors: Li
authors: Katherine H
authors: KH
authors: Fegan
authors: Gordon J
authors: GJ
authors: Hildick-Smith
authors: Dhvanit I
authors: DI
authors: Shah
authors: Jeffrey D
authors: JD
authors: Cooney
authors: Wen
authors: W
authors: Chen
authors: Matthew J
authors: MJ
authors: King
authors: Yvette Y
authors: YY
authors: Yien
authors: Iman J
authors: IJ
authors: Schultz
authors: Heidi
authors: H
authors: Anderson
authors: Arthur J
authors: AJ
authors: Dalton
authors: Matthew L
authors: ML
authors: Freedman
authors: Paul D
authors: PD
authors: Kingsley
authors: James
authors: J
authors: Palis
authors: Shilpa M
authors: SM
authors: Hattangadi
authors: Harvey F
authors: HF
authors: Lodish
authors: Diane M
authors: DM
authors: Ward
authors: Jerry
authors: J
authors: Kaplan
authors: Takahiro
authors: T
authors: Maeda
authors: Prem
authors: P
authors: Ponka
authors: Barry H
authors: BH
authors: Paw
mesh_terms: D000704:Analysis of Variance; D000740:Anemia / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016650:Fluorescein-5-isothiocyanate; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D007501:Iron / Q000378:metabolism*; D051379:Mice; D011990:Receptors, Transferrin / Q000378:metabolism*; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D011990:Receptors, Transferrin; C533230:Snx3 protein, mouse; D058305:Sorting Nexins; D007501:Iron; D016650:Fluorescein-5-isothiocyanate