Glycosyl phosphatidylinositol membrane anchoring of melanotransferrin (p97): apical compartmentalization in intestinal epithelial cells.
Melanotransferrin (p97) is an iron-binding membrane glycoprotein with 40% homology to transferrin and lactoferrin. It was first identified on the basis of its high level of expression in melanoma cells, as compared to normal melanocytes. It is also present in many cultured cell types. In normal tissues, p97 is expressed in fetal intestine, umbilical cord, sweat gland ducts and liver sinusoidal lining cells. Kinetic studies in melanoma cells have suggested that p97 plays a role in iron metabolism. We have examined expression of p97 in cell lines derived from human colorectal carcinomas which express a differentiated phenotype. When polarized, these cells showed a preferred apical distribution of p97, as demonstrated by immunohistochemistry, immune electron microscopy and domain-selective biotinylation. Correspondingly, p97 was only found on the apical brush border of epithelial cells in the fetal intestine. p97 was shown to be anchored to the membrane through a glycosyl phosphatidylinositol moiety by treatment with phophatidylinositol-specific phospholipase C (PI-PLC) and labeling with [14C]ethanolamine. These observations provide a basis for the elucidation of the physiological role of p97 in iron metabolism and its possible role in cell proliferation and malignant cell transformation.
Alemany
R
R
Department d'Immunologia, Universitat de Barcelona, Spain.
Vilá
M R
MR
Francí
C
C
Egea
G
G
Real
F X
FX
Thomson
T M
TM
D000951:Antigens, Neoplasm; D002451:Cell Compartmentation / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000737:chemistry; D004847:Epithelial Cells; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D017261:Glycosylphosphatidylinositols; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins