Chaperone turns gatekeeper: PCBP2 and DMT1 form an iron-transport pipeline

摘要

How is cellular iron (Fe) uptake and efflux regulated in mammalian cells? In this issue of the Biochemical Journal,Yanatori et al. report for the first time that a member ofthe emerging PCBP [poly(rC)-binding protein] Fe-chaperone family, PCBP2, physically interacts with the major Fe importer DMT1 (divalent metal transporter 1) and the Fe exporter FPN1(ferroportin 1). In both cases, the interaction of the Fe transporter with PCBP2 is Fe-dependent. Interestingly, another PCBP Fe chaperone, PCBP1, does not appear to bind to DMT1. Strikingly,the PCBP2–DMT1 interaction is required for DMT1-dependentcellular Fe uptake, suggesting that, in addition to functioning as an intracellular Fe chaperone, PCBP2 may be a molecular ‘gatekeeper’ for transmembrane Fe transport. These new data hint at thepossibility that PCBP2 may be a component of a yet-to-bedescribed Fe-transport metabolon that engages in Fe channellingto and from Fe transporters and intracellular sites.