creators_name: Sheokand, Navdeep
creators_name: Malhotra, Himanshu
creators_name: Kumar, Santosh
creators_name: Tillu, Vikas A
creators_name: Chauhan, Anoop S
creators_name: Raje, Chaaya Iyengar
creators_name: Raje, Manoj
type: article
datestamp: 2015-01-27 09:35:23
lastmod: 2015-01-27 09:35:23
metadata_visibility: show
title: Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells.
ispublished: pub
subjects: QR
keywords: Apotransferrin; Ferroportin; GAPDH; Higher order multifunctional protein; Iron export; Receptor
abstract: Iron (Fe(2+), Fe(3+)) 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 iron-depleted cells recruit glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a multitasking, 'moonlighting' protein, to their surface for internalization of the iron carrier holotransferrin. Here, we report that under the converse condition of intracellular iron excess, cells switch the isoform of GAPDH on their surface to one that now recruits iron-free apotransferrin in close association with ferroportin to facilitate the efflux of iron. Increased expression of surface GAPDH correlated with increased apotransferrin binding and enhanced iron export from cells, a capability lost in GAPDH-knockdown cells. These findings were confirmed in vivo utilizing a rodent model of iron overload. Besides identifying for the first time an apotransferrin receptor, our work uncovers the two-way switching of multifunctional molecules to manage cellular micronutrient requirements.
date: 2014-10-01
date_type: published
publication: Journal of cell science
volume: 127
number: Pt 19
publisher: Cambridge : Company of Biologists
pagerange: 4279-91
refereed: TRUE
issn: 1477-9137
official_url: http://jcs.biologists.org/content/127/19/4279.long
citation:   Sheokand, Navdeep and Malhotra, Himanshu and Kumar, Santosh and Tillu, Vikas A and Chauhan, Anoop S and Raje, Chaaya Iyengar and Raje, Manoj  (2014) Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells.  Journal of cell science, 127 (Pt 19).  pp. 4279-91.  ISSN 1477-9137