Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells

@article{Sheokand2014MoonlightingCG,
  title={Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells},
  author={Navdeep Sheokand and Himanshu Malhotra and Santosh Kumar and Vikas A Tillu and Anoop Singh Chauhan and Chaaya Iyengar Raje and Manoj Raje},
  journal={Journal of Cell Science},
  year={2014},
  volume={127},
  pages={4279 - 4291}
}
ABSTRACT Iron (Fe2+, Fe3+) homeostasis is a tightly regulated process, involving precise control of iron influx and egress from cells. Although the mechanisms of its import into cells by iron carrier molecules are well characterized, iron export remains poorly understood. The current paradigm envisages unique functions associated with specialized macromolecules for its cellular import (transferrin receptors) or export (ferroportin, also known as SLC40A1). Previous studies have revealed that… Expand
Reverse overshot water-wheel retroendocytosis of apotransferrin extrudes cellular iron
TLDR
Evidence is presented that retroendocytosis of apotransferrin mediated by multifunctional GAPDH extrudes excess cellular Fe in a mechanism reminiscent of pumping out of water by a reverse overshot water-wheel. Expand
Protein moonlighting in iron metabolism: glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
Iron is essential for the survival of both prokaryotic and eukaryotic organisms. It functions as a cofactor for several vital enzymes and iron deprivation is fatal to cells. However, at the sameExpand
The Role of Moonlighting GAPDH in Membrane Structure and Function: Membrane Fusion and Iron Metabolism
TLDR
Findings highlight the interrelationship between membrane function and moonlighting GAPDH activity and indicate its requirement for membrane fusion and for basic mechanisms of receptor-mediated iron metabolism. Expand
Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells
TLDR
This is the first study demonstrating the novel interaction between multifunctional GAPDH and the phagocytic receptor CD14 resulting in apoptotic cell clearance (efferocytosis). Expand
Moonlighting glycolytic protein glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH): an evolutionarily conserved plasminogen receptor on mammalian cells
  • A. S. Chauhan, Manoj Kumar, +6 authors M. Raje
  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2017
TLDR
It is demonstrated that upon inflammation, macrophages recruit GAPDH onto their surface to carry out the same task of capturing Plg to digest ECM to aid rapid phagocyte migration and combat the invading pathogens. Expand
Transferrin receptor 1 controls systemic iron homeostasis by fine-tuning hepcidin expression to hepatocellular iron load.
TLDR
It is concluded that Tfr1 is redundant for basal hepatocellular iron supply but essential for fine-tuning hepcidin responses according to the iron load of hepatocytes, and that TfrcAlb-Cre mice appropriately regulate Hamp expression following dietary iron manipulations or holo-transferrin injection. Expand
Evolutionary Perspectives on the Moonlighting Functions of Bacterial Factors That Support Actin-Based Motility
TLDR
It is proposed that intracellular ABM functions have evolved from ancestral, extracellular adhesin functions, such as bacterial aggregation, biofilm formation, and host cell adhesion/invasion. Expand
Unconventional Transport Routes of Soluble and Membrane Proteins and Their Role in Developmental Biology
TLDR
The main aim of the meeting was to include the highest number of topics, summarized in this report, related to the unconventional transport routes of protein and membranes, and these alternative pathways are functionally related to biotic stress and development. Expand
Critical protein GAPDH and its regulatory mechanisms in cancer cells
TLDR
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is tightly regulated at transcriptional and posttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Expand
Iron Homeostasis and Trypanosoma brucei Associated Immunopathogenicity Development: A Battle/Quest for Iron
TLDR
An overview of how parasites acquire iron from the host and how iron modulation of the host MYPS affects trypanosomosis-associated anemia development is given. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 79 REFERENCES
Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition.
TLDR
This research uncovers a hidden and primitive pathway of bulk iron trafficking involving a secreted receptor that is a multifunctional glycolytic enzyme that has implications in pathological conditions such as infectious diseases and cancer. Expand
Role of Ceruloplasmin in Macrophage Iron Efflux during Hypoxia*
TLDR
Data show that Cp stimulates iron release from macrophages under hypoxic conditions by a ferroxidase-dependent mechanism, possibly involving generation of a negative iron gradient. Expand
Murine macrophages response to iron.
TLDR
This study represents an example of the potential usefulness of "integarated omics" in the field of iron biology, especially for the elucidation of the molecular mechanisms controlling iron homeostasis in normal and disease conditions. Expand
The Macrophage Cell Surface Glyceraldehyde-3-phosphate Dehydrogenase Is a Novel Transferrin Receptor*
TLDR
It is shown for the first time that the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is localized on human and murine macrophage cell surface and interacts with transferrin and the GAPDH-transferrin complex is subsequently internalized into the early endosomes. Expand
Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin.
TLDR
Observations are consistent with a direct iron export by ferroportin through the plasma membrane of macrophages and strongly support an efficient posttranscriptional down-regulation of ferro portin by hepcidin in these cells. Expand
Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin.
TLDR
FPN1 is directly involved in the export of iron during erythrocyte-iron recycling by macrophages, consistent with a role in the recycling of iron from senescent red cells. Expand
Hepcidin targets ferroportin for degradation in hepatocytes
TLDR
Hepcidin can trigger ferroportin degradation in hepatocytes, which must be taken into account when considering hepcidin therapeutics, which is shown to support the centrolobular iron deposition observed in mice. Expand
Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor.
TLDR
It is demonstrated that upon iron depletion, GAPDH functions as a preferred receptor for transferrin rather than TfR1 in some but not all cell types, and the kinetics of this pathway appear to be a low affinity, high capacity, recycling pathway wherein transferrin is catabolised. Expand
The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor.
TLDR
It is reported that the multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) functions as a novel receptor for lactoferrin (Lf) in macrophages and that upon iron depletion the binding of lact oferrin to macrophage cell surface is enhanced. Expand
Iron metabolism in the mononuclear phagocyte system
TLDR
Recent studies characterizing the function and regulation of natural resistance-associated macrophage protein 1 (Nramp1), divalent metal transporter 1 (DMT1), HLA-linked hemechromatosis gene (HFE), ferroportin 1 (FPN1), and hepcidin are rapidly expanding knowledge on the molecular level of MPS iron handling. Expand
...
1
2
3
4
5
...