TY  - JOUR
ID  - open1531
UR  - http://jcs.biologists.org/content/127/19/4279.long
IS  - Pt 19
A1  - Sheokand, Navdeep
A1  - Malhotra, Himanshu
A1  - Kumar, Santosh
A1  - Tillu, Vikas A
A1  - Chauhan, Anoop S
A1  - Raje, Chaaya Iyengar
A1  - Raje, Manoj
Y1  - 2014/10/01/
N2  - 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.
PB  - Cambridge : Company of Biologists
JF  - Journal of cell science
VL  - 127
KW  - Apotransferrin; Ferroportin; GAPDH; Higher order multifunctional protein; Iron export; Receptor
SN  - 1477-9137
TI  - Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells.
SP  - 4279
EP  - 91
ER  -