Ferritoid, a tissue-specific nuclear transport protein for ferritin in corneal epithelial cells.
Previously we reported that ferritin in corneal epithelial (CE) cells is a nuclear protein that protects DNA from UV damage. Since ferritin is normally cytoplasmic, in CE cells, a mechanism must exist that effects its nuclear localization. We have now determined that this involves a nuclear transport molecule we have termed ferritoid. Ferritoid is specific for CE cells and is developmentally regulated. Structurally, ferritoid contains multiple domains, including a functional SV40-type nuclear localization signal and a ferritin-like region of approximately 50% similarity to ferritin itself. This latter domain is likely responsible for the interaction between ferritoid and ferritin detected by co-immunoprecipitation analysis. To test functionally whether ferritoid is capable of transporting ferritin into the nucleus, we performed cotransfections of COS-1 cells with constructs for ferritoid and ferritin. Consistent with the proposed nuclear transport function for ferritoid, co-transfections with full-length constructs for ferritoid and ferritin resulted in a preferential nuclear localization of both molecules; this was not observed when the nuclear localization signal of ferritoid was deleted. Moreover, since ferritoid is structurally similar to ferritin, it may be an example of a nuclear transporter that evolved from the molecule it transports (ferritin).
Millholland
John M
JM
Department of Anatomy and Cellular Biology, Tufts University Medical School, Boston, Massachusetts 02111, USA.
Fitch
John M
JM
Cai
Cindy X
CX
Gibney
Eileen P
EP
Beazley
Kelly E
KE
Linsenmayer
Thomas F
TF
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002642:Chick Embryo; D018076:DNA, Complementary / Q000302:isolation & purification; D019573:Epithelium, Corneal / Q000166:cytology*; D005293:Ferritins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection
D002352:Carrier Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D005293:Ferritins