Characterization of nuclear ferritin and mechanism of translocation.
Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in cell nuclei. It is an established fact that H-ferritin is the major form of nuclear ferritin, but little is known about the roles of ferritin in nuclei or about the mechanisms that control its appearance within the nuclear volume. In the present study, we show that, for human SW1088 astrocytoma cells, the nuclear and cytoplasmic forms of H-ferritin are products of the same mRNA. Histochemical and biochemical evidence is presented showing that ferritin is distributed non-randomly within the nuclear volume and that it preferentially associates with heterochromatin. Both cytoplasmic and nuclear populations of H-ferritin contain mixtures of non- and O-glycosylated forms, but the nuclear population is enriched in O-glycosylated forms. Cells treated with alloxan, a potent inhibitor of O-glycosylation, contained significantly less nuclear ferritin compared with cells grown in control media. Alloxan inhibited the reappearance of H-ferritin in nuclei of cells released from conditions of iron depletion, but did not prevent its disappearance from nuclei of cells undergoing iron depletion. These results suggest that O-glycosylation accompanies the transfer of ferritin from the cytoplasm to the nucleus, but does not influence the reverse process. The picture that emerges is one in which ferritin translocation between the cytoplasm and the nucleus is post-translationally regulated and responds to environmental and nutritional cues.
Surguladze
Nodar
N
Department of Neurosurgery, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Patton
Stephanie
S
Cozzi
Anna
A
Fried
Michael G
MG
Connor
James R
JR
D021581:Active Transport, Cell Nucleus; D000496:Alloxan / Q000494:pharmacology; D001052:Apoferritins; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D021122:Protein Subunits; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D021122:Protein Subunits; D012333:RNA, Messenger; D000496:Alloxan; D005293:Ferritins; D001052:Apoferritins; D007501:Iron; D003851:Deoxyribonucleases