title: The macrophage cell surface glyceraldehyde-3-phosphate dehydrogenase is a novel transferrin receptor.
abstract: The reticuloendothelial system plays a major role in iron metabolism. Despite this, the manner in which macrophages handle iron remains poorly understood. Mammalian cells utilize transferrin-dependent mechanisms to acquire iron via transferrin receptors 1 and 2 (TfR1 and TfR2) by receptor-mediated endocytosis. Here, we show for the first time that the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is localized on human and murine macrophage cell surface. The expression of this surface GAPDH is regulated by the availability of iron in the medium. We further demonstrate that this GAPDH interacts with transferrin and the GAPDH-transferrin complex is subsequently internalized into the early endosomes. Our work sheds new light on the mechanisms involved in regulation of iron, vital for controlling numerous diseases and maintaining normal immune function. Thus, we propose an entirely new avenue for investigation with respect to transferrin uptake and regulation mechanisms in macrophages.
authors.affiliation: Institute of Microbial Technology, Sector 39-A, Chandigarh-160036, India.
authors.forename: Chaaya Iyengar
authors.initials: CI
authors.lastname: Raje
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Arti
authors.initials: A
authors.lastname: Harle
authors.forename: Jagpreet Singh
authors.initials: JS
authors.lastname: Nanda
authors.forename: Manoj
authors.initials: M
authors.lastname: Raje
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D004705:Endocytosis; D005434:Flow Cytometry; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011990:Receptors, Transferrin / Q000502:physiology*
chemical_list: D011990:Receptors, Transferrin; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)