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J. Biol. Chem., Vol. 282, Issue 5, 3252-3261, February 2, 2007

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The Macrophage Cell Surface Glyceraldehyde-3-phosphate Dehydrogenase Is a Novel Transferrin Receptor^*

From the Institute of Microbial Technology, Sector 39-A, Chandigarh-160036, India

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.

Received for publication, August 31, 2006 , and in revised form, October 20, 2006.

^* This work was supported in part by Department of Science and Technology, Government of India. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ Recipient of DST Grant SR/WOS-A/LS-86/2006.

² Recipient of a CSIR Junior Research Fellowship.

³ To whom correspondence should be addressed: Inst. of Microbial Technology, Sector 39-A, Chandigarh-160036, India. Tel.: 091-0172-2695215; Fax: 091-172-2690632; E-mail: manoj{at}imtech.res.in.

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