Human MRCKalpha is regulated by cellular iron levels and interferes with transferrin iron uptake.
Myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha, 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 MRCKalpha protein expression is also regulated by iron levels; MRCKalpha colocalizes with transferrin (Tf)-loaded transferrin receptors (TfR), and attenuation of MRCKalpha expression by a short hairpin RNA silencing construct leads to a significant decrease in Tf-mediated iron uptake. Our results thus indicate that MRCKalpha 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 MRCKalpha activity by intracellular iron levels could thus represent another molecular feedback mechanism cells could use to finely tune iron uptake to actual needs.
Cmejla
Radek
R
Institute of Hematology and Blood Transfusion, Department of Cell Physiology, U Nemocnice 1, Prague 128 20, Czech Republic.
Ptackova
Pavlina
P
Petrak
Jiri
J
Savvulidi
Filipp
F
Cerny
Jan
J
Sebesta
Ondrej
O
Vyoral
Daniel
D
D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron; C105518:CDC42BPA protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases