Human MRCKα is regulated by cellular iron levels and interferes with transferrin iron uptake

Myotonic dystrophy kinase-related Cdc42-binding kinase α (MRCKα, formally known as CDC42BPA) is a serine/threonine kinase that can regulate actin/myosin assembly and activity. Recently, it has been shown that it possesses a functional iron responsive element (IRE) in the 3′-untranslated region (UTR) of its mRNA, suggesting that it may be involved in iron metabolism. Here we report that MRCKα protein expression is also regulated by iron levels; MRCKα colocalizes with transferrin (Tf)-loaded transferrin receptors (TfR), and attenuation of MRCKα expression by a short hairpin RNA silencing construct leads to a significant decrease in Tf-mediated iron uptake. Our results thus indicate that MRCKα takes part in Tf-iron uptake, probably via regulation of Tf–TfR endocytosis/endosome trafficking that is dependent on the cellular cytoskeleton. Regulation of the MRCKα activity by intracellular iron levels could thus represent another molecular feedback mechanism cells could use to finely tune iron uptake to actual needs.