title: Secreted multifunctional Glyceraldehyde-3-phosphate dehydrogenase sequesters lactoferrin and iron into cells via a non-canonical pathway.
abstract: Lactoferrin is a crucial nutritionally important pleiotropic molecule and iron an essential trace metal for all life. The current paradigm is that living organisms have evolved specific membrane anchored receptors along with iron carrier molecules for regulated absorption, transport, storage and mobilization of these vital nutrients. We present evidence for the existence of non-canonical pathway whereby cells actively forage these vital resources from beyond their physical boundaries, by secreting the multifunctional housekeeping enzyme Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) into the extracellular milieu. This effect's an autocrine/paracrine acquisition of target ligand into the cell. Internalization by this route is extensively favoured even by cells that express surface receptors for lactoferrin and involves urokinase plasminogen activator receptor (uPAR). We also demonstrate the operation of this phenomenon during inflammation, as an arm of the innate immune response where lactoferrin denies iron to invading microorganisms by chelating it and then itself being sequestered into surrounding host cells by GAPDH.
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Anoop S
authors.initials: AS
authors.lastname: Chauhan
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Pooja
authors.initials: P
authors.lastname: Rawat
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Malhotra
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Sheokand
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Anil
authors.initials: A
authors.lastname: Patidar
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Surbhi
authors.initials: S
authors.lastname: Chaudhary
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Jakhar
authors.affiliation: National Institute of Pharmaceutical Education &Research, Phase X, Sector 67, SAS Nagar, INDIA-160062 Punjab.
authors.forename: Chaaya I
authors.initials: CI
authors.lastname: Raje
authors.affiliation: Institute of Microbial Technology, CSIR, Sector 39A, INDIA-160036 Chandigarh.
authors.forename: Manoj
authors.initials: M
authors.lastname: Raje
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004386:Duodenum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D005110:Extracellular Space / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator; D007501:Iron; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007781:Lactoferrin