Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells

Sheokand, Navdeep, Malhotra, Himanshu, Kumar, Santosh, Tillu, Vikas A., Chauhan, Anoop S., Raje, Chaaya I. and Raje, Manoj (2014) Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells. Journal of Cell Science, 127 19: 4279-4291. doi:10.1242/jcs.154005

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Author Sheokand, Navdeep
Malhotra, Himanshu
Kumar, Santosh
Tillu, Vikas A.
Chauhan, Anoop S.
Raje, Chaaya I.
Raje, Manoj
Title Moonlighting cell-surface GAPDH recruits apotransferrin to effect iron egress from mammalian cells
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 1477-9137
Publication date 2014-09-30
Year available 2014
Sub-type Article (original research)
DOI 10.1242/jcs.154005
Open Access Status File (Publisher version)
Volume 127
Issue 19
Start page 4279
End page 4291
Total pages 13
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Language eng
Formatted abstract
Iron (Fe2+, Fe3+) 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.
Keyword Apotransferrin
Higher order multifunctional protein
Iron export
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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