Reactome | SLC22A17 binds LCN2:2,5DHBA:Fe3+

SLC22A17 binds LCN2:2,5DHBA:Fe3+

Stable Identifier

R-HSA-5246444

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region, cytosol

ReviewStatus

5/5

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Neutrophil gelatinase-associated lipocalin (LCN2, NGAL) is a member of the lipocalin superfamily that is involved in iron trafficking both in and out of cells (Goetz et al. 2002). LCN2 binds iron through association with 2,5-dihydroxybenzoic acid (2,5DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. The iron-bound form of LCN2 (holo-LCN2) is internalised following binding to the solute carrier family 22 member 17 (SLC22A17) receptor, leading to release of iron which increases intracellular iron concentration and subsequent inhibition of apoptosis. This step is inferred from experiments using the highly homologous 24p3 mouse lipocalin and 24p3R mouse cell surface receptor (Devireddy et al. 2005). During infection, bacteria scavenge iron from the host cell and transfer it to the pathogen cell. Upon encountering invading bacteria, Toll-like receptors on immune cells can stimulate the transcription, translation and secretion of LCN2. LCN2 can then limit bacterial growth by sequestrating the iron-laden siderophore so this event is pivotal in the innate immune response to bacterial infection (Flo et al. 2004).

Literature References

PubMed ID	Title	Journal	Year
12453412	The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition Goetz, DH, Holmes, MA, Borregaard, N, Bluhm, ME, Raymond, KN, Strong, RK	Mol. Cell	2002
16377569	A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake Devireddy, LR, Gazin, C, Zhu, X, Green, MR	Cell	2005
15531878	Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron Flo, TH, Smith, KD, Sato, S, Rodriguez, DJ, Holmes, MA, Strong, RK, Akira, S, Aderem, A	Nature	2004