title: Iron uptake mediated by binding of H-ferritin to the TIM-2 receptor in mouse cells.
abstract: Ferritin binds specifically and saturably to a variety of cell types, and recently several ferritin receptors have been cloned. TIM-2 is a specific receptor for H ferritin (HFt) in the mouse. TIM-2 is a member of the T cell immunoglobulin and mucin domain containing (TIM) protein family and plays an important role in immunity. The expression of TIM-2 outside of the immune system indicates that this receptor may have broader roles. We tested whether ferritin binding to TIM-2 can serve as an iron delivery mechanism. TIM-2 was transfected into normal (TCMK-1) mouse kidney cells, where it was appropriately expressed on the cell surface. HFt was labeled with (55)Fe and (55)Fe-HFt was incubated with TIM-2 positive cells or controls. (55)Fe-HFt uptake was observed only in TIM-2 positive cells. HFt uptake was also seen in A20 B cells, which express endogenous TIM-2. TIM-2 levels were not increased by iron chelation. Uptake of (55)Fe-HFt was specific and temperature-dependent. HFt taken up by TIM-2 positive cells transited through the endosome and eventually entered a lysosomal compartment, distinguishing the HFt pathway from that of transferrin, the classical vehicle for cellular iron delivery. Iron delivered following binding of HFt to TIM-2 entered the cytosol and became metabolically available, resulting in increased levels of endogenous intracellular ferritin. We conclude that TIM-2 can function as an iron uptake pathway.
authors: Department of Biology, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.
authors: Jian
authors: J
authors: Han
authors: William E
authors: WE
authors: Seaman
authors: Xiumin
authors: X
authors: Di
authors: Wei
authors: W
authors: Wang
authors: Mark
authors: M
authors: Willingham
authors: Frank M
authors: FM
authors: Torti
authors: Suzy V
authors: SV
authors: Torti
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000378:metabolism*; D001692:Biological Transport; D011992:Endosomes / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C442242:Timd2 protein, mouse; D001052:Apoferritins; D007501:Iron