Document Detail


Complete inhibition of transferrin recycling by monensin in K562 cells.
MedLine Citation:
PMID:  6094573     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Monensin blocks human transferrin recycling in a dose-dependent and reversible manner in K562 cells, reaching 100% inhibition at a noncytocidal dose of 10(-5) M, whereas transferrin recycling is virtually unaffected by noncytocidal doses of chloroquine. The intracellular pathway of human transferrin in K562 cells, both in the presence and absence of 10(-5) M monensin, was localized by indirect immunofluorescence. Monensin blocks transferrin recycling by causing internalized ligand to accumulate in the perinuclear region of the cell. The effect of 10(-5) M monensin on human transferrin kinetics was quantitatively measured by radioimmunoassay and showed a positive correlation with immunofluorescent studies. Immunoelectron microscopic localization of human transferrin as it cycles through K562 cells reveals the appearance of perinuclear transferrin-positive multivesicular bodies within 3 min of internalization, with subsequent exocytic delivery of the ligand to the cell surface via transferrin-staining vesicles arising from these perinuclear structures within 5 min of internalization. Inhibition of ligand recycling with 10(-5) M monensin causes dilated transferrin-positive multivesicular bodies to accumulate within the cell with no evidence of recycling vesicles. A coordinated interaction between multivesicular bodies and the Golgi apparatus appears to be involved in the recycling of transferrin in K562 cells. Cell-surface-binding sites for transferrin were reduced by 50% with 10(-5) M monensin treatment; however, this effect was not attenuated by 80% protein synthesis inhibition with cycloheximide, supporting the idea that the transferrin receptor is also recycled through the Golgi.
Authors:
B S Stein; K G Bensch; H H Sussman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  259     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1984 Dec 
Date Detail:
Created Date:  1985-01-10     Completed Date:  1985-01-10     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14762-72     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Chloroquine / pharmacology
Fluorescent Antibody Technique
Furans / pharmacology*
Humans
Kinetics
Leukemia, Myeloid, Acute
Microscopy, Electron
Monensin / pharmacology*
Receptors, Cell Surface / analysis,  metabolism*
Receptors, Transferrin
Transferrin / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
CA09151/CA/NCI NIH HHS; CA13533/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Furans; 0/Receptors, Cell Surface; 0/Receptors, Transferrin; 11096-37-0/Transferrin; 17090-79-8/Monensin; 54-05-7/Chloroquine

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