Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor

Kumar, Santosh; Sheokand, Navdeep; Mhadeshwar, Mayur Anant; Raje, Chaaya Iyengar; Raje, Manoj

doi:10.1016/j.biocel.2011.10.016

Cited by 50 publications

(69 citation statements)

References 54 publications

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“…5B). This value is much higher than that reported for internalization of holotransferrin through GAPDH in the same cells (Kumar et al, 2012). It is also higher than the value obtained previously for holotransferrin internalization through transferrin receptor protein 1 (TfR1), determined using CHO cells (Johnson et al, 1994).…”

Section: Resultscontrasting

confidence: 67%

“…We also obtained comparable recycling rates of 0.18± 0.017 min −1 and 0.195±0.039 min −1 for receptor and ligand, respectively. These values are also distinct from the recycling rates of the holotransferrin GAPDH receptor characterized earlier (Kumar et al, 2012) and from the well-described TfR1 (Johnson et al, 1994). The closely matching values suggest that the internalization and recycling of the two partners (apotransferrin and cell surface GAPDH) are coupled.…”

Section: Resultsmentioning

confidence: 45%

“…THP1 cells were activated through incubation with 12.5 ng/ml of phorbol 12-myristate 13-acetate (PMA) for 24 h. A stable THP1 cell line in which knockdown of total cellular GAPDH (by using GAPDH shRNA lentiviral particles) has been established previously (Sheokand et al, 2013) was used in the study. CHO-TRVb cells were silenced for GAPDH expression (by using GAPDH siRNA), as described previously (Kumar et al, 2012). All primary cells (hepatocytes, bone marrow, spleen macrophages and spleen lymphocytes) were obtained from Sprague Dawley rat or Balb/c mice, as described previously.…”

Section: Cell Lines Primary Cells and Materialsmentioning

confidence: 99%

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Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron

Sheokand

Malhotra

Chauhan

et al. 2016

Journal of Cell Science

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Iron a vital micronutrient for all organisms must be managed judiciously as both, deficiency or excess can trigger severe pathology. While cellular iron import is well understood its export is thought to be limited to transmembrane extrusion via ferroportin the only known mammalian iron exporter. Utilizing primary cells and cell lines (including those with no discernible expression of ferroportin on their surface) we demonstrate that upon iron loading the multifunctional enzyme Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that is recruited to the cell surface treadmills apo transferrin (apo Tf) in and out of the cell. Kinetic analysis utilizing; labeled ligand, GAPDH knock down cells, Fe55 labeled cells and pharmacological inhibitors of endocytosis confirmed GAPDH dependent apo Tf internalization as a prerequisite for cellular iron export. These studies define an unusual rapid recycling process of retroendocytosis for cellular iron extrusion, a process mirroring receptor mediated internalization that has never before been considered for maintenance of cellular cationic homeostasis. Modulation of this unusual pathway could provide insights for management of iron overload disorders.

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Section: Resultscontrasting

confidence: 67%

Section: Resultsmentioning

confidence: 45%

Section: Cell Lines Primary Cells and Materialsmentioning

confidence: 99%

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Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron

Sheokand

Malhotra

Chauhan

et al. 2016

Journal of Cell Science

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“…We selected GAPDH for further analysis because: (i) GAPDH has recently been identified as a transferrin receptor in macrophages and numerous other cell types [26][27][28] , (ii) the highly conserved nature of the protein and (iii) its role as a virulence factor [29][30][31][32] .…”

Section: Resultsmentioning

confidence: 99%

“…GAPDH has also been reported as a transferrin-binding protein in S. aureus and S. epidermidis 21 . In eukaryotes, numerous functions have been attributed to GAPDH including its role as a receptor for transferrin in different cell types and especially in macrophages [26][27][28]39 . Since this molecule is highly conserved across species (B50% identity with human GAPDH), we initially selected GAPDH to further explore the role of this transferrinbinding protein in M.tb.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

et al. 2014

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Mycobacterium tuberculosis (M.tb), which requires iron for survival, acquires this element by synthesizing iron-binding molecules known as siderophores and by recruiting a host iron-transport protein, transferrin, to the phagosome. The siderophores extract iron from transferrin and transport it into the bacterium. Here we describe an additional mechanism for iron acquisition, consisting of an M.tb protein that drives transport of human holo-transferrin into M.tb cells. The pathogenic strain M.tb H37Rv expresses several proteins that can bind human holo-transferrin. One of these proteins is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Rv1436), which is present on the surface of M.tb and its relative Mycobacterium smegmatis. Overexpression of GAPDH results in increased transferrin binding to M.tb cells and iron uptake. Human transferrin is internalized across the mycobacterial cell wall in a GAPDH-dependent manner within infected macrophages.

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Protein Moonlighting and Human Health and Idiopathic Human Disease

2016

Protein Moonlighting in Biology and Medicine

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Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor

Cited by 50 publications

References 54 publications

Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron

Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

Protein Moonlighting and Human Health and Idiopathic Human Disease

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