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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor.
 
Creator Kumar, Santosh
Sheokand, Navdeep
Mhadeshwar, Mayur Anant
Raje, Chaaya Iyengar
Raje, Manoj
 
Subject QD Chemistry
 
Description A majority of cells obtain of transferrin (Tf) bound iron via transferrin receptor 1 (TfR1) or by transferrin receptor 2 (TfR2) in hepatocytes. Our study establishes that cells are capable of acquiring transferrin iron by an alternate pathway via GAPDH. These findings demonstrate that upon iron depletion, GAPDH functions as a preferred receptor for transferrin rather than TfR1 in some but not all cell types. We utilized CHO-TRVb cells that do not express TfR1 or TfR2 as a model system. A knockdown of GAPDH in these cells resulted in a decrease of not only transferrin binding but also associated iron uptake. The current study also demonstrates that, unlike TfR1 and TfR2 which are localized to a specific membrane fraction, GAPDH is located in both the detergent soluble and lipid raft fractions of the cell membrane. Further, transferrin uptake by GAPDH occurs by more than one mechanism namely clathrin mediated endocytosis, lipid raft endocytosis and macropinocytosis. By determining the kinetics of this pathway it appears that GAPDH-Tf uptake is a low affinity, high capacity, recycling pathway wherein transferrin is catabolised. Our findings provide an explanation for the detailed role of GAPDH mediated transferrin uptake as an alternate route by which cells acquire iron.
 
Publisher Elsevier Science
 
Date 2011-11-02
 
Type Article
PeerReviewed
 
Relation http://www.sciencedirect.com/science/article/pii/S1357272511002895
http://crdd.osdd.net/open/441/
 
Identifier Kumar, Santosh and Sheokand, Navdeep and Mhadeshwar, Mayur Anant and Raje, Chaaya Iyengar and Raje, Manoj (2011) Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor. The international journal of biochemistry & cell biology. ISSN 1878-5875 (In Press)