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Lipid raft‐dependent endocytosis of metallothionein in HepG2 cells
Author(s) -
Hao Qiang,
Hong SungHye,
Maret Wolfgang
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20874
Subject(s) - endocytosis , lipid raft , raft , metallothionein , chemistry , microbiology and biotechnology , lipid droplet , biophysics , biochemistry , cell , biology , polymerization , organic chemistry , gene , polymer
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‐β‐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. J. Cell. Physiol. 210: 428–435, 2007. © 2006 Wiley‐Liss, Inc.