Lipid raft-dependent endocytosis of metallothionein in HepG2 cells.
Human hepatocellular carcinoma (HepG2) cells take up metallothionein (MT) by endocytosis. MT co-localizes with albumin but not with transferrin, indicating uptake via a non-classical pathway rather than via clathrin-mediated endocytosis. A lipid raft-dependent uptake is indicated by pravastatin inhibition of cholesterol synthesis and methyl-beta-cyclodextrin inhibition of cholesterol translocation to the plasma membrane, reducing MT uptake by 29% and 69%, respectively. Subcellular fractionation after MT uptake reveals significant amounts of MT in vesicular fractions including lysosomes but virtually no MT in the cytosol. Metals bound to MT are released into the cytosol, however. The findings define a pathway for cellular metal acquisition. Together with results from other studies demonstrating secretion of MT from different cells and the presence of MT in extracellular fluids, the results suggest a function of MT in intercellular communication.
Hao
Qiang
Q
Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
Hong
Sung-Hye
SH
Maret
Wolfgang
W
D002450:Cell Communication / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003600:Cytosol / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D045604:Extracellular Fluid / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D021962:Membrane Microdomains / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008670:Metals; D011500:Protein Synthesis Inhibitors; D008668:Metallothionein; D002784:Cholesterol