Document Detail

Altered role of microtubules in asialoglycoprotein trafficking in developing liver.
MedLine Citation:
PMID:  2301574     Owner:  NLM     Status:  MEDLINE    
Efficient receptor-mediated endocytosis of asialoglycoprotein by mature liver requires participation of microtubules that convey newly internalized ligand to lysosomes for degradation and receptor back to plasma membrane to continue endocytosis. To ascertain whether microtubular participation in asialoglycoprotein endocytosis is altered during development, we compared endocytosis of 125I-labeled asialoorosomucoid (ASOR) in neonatal rat hepatocytes to that in adult cells, with and without microtubular disruption by colchicine. Control experiments demonstrated that 125I-ASOR degradation in neonatal hepatocytes occurred at 70% of the adult rate during continuous endocytosis, although neonatal surface receptors were only approximately 40% as numerous. Colchicine disruption of microtubules reduced 125I-ASOR degradation and steady-state intracellular ASOR more in adults during continuous endocytosis. Degradation of 125I-ASOR prebound to surface receptors was equally impaired by colchicine in the two groups. Continuous ASOR endocytosis by colchicine-treated adult hepatocytes progressively depleted their surface receptors but minimally in neonates. Unlike colchicine, the protonophore monensin markedly impaired receptor recycling as well as postinternalization ligand trafficking in both neonates and adults. Thus these experiments demonstrate that asialoglycoprotein processing proceeds as efficiently in neonatal as in adult hepatocytes despite a reduced surface receptor population. Microtubules are required to maintain receptors on cell surface as well as for postinternalization trafficking in adult cells. During development, only the latter process substantially requires microtubules, indicating that microtubular participation in protein trafficking is selectively, not uniformly, diminished at this time in life.
S S Kaufman; P L Blain; J H Park; D J Tuma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  258     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1990 Jan 
Date Detail:
Created Date:  1990-03-01     Completed Date:  1990-03-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  G129-37     Citation Subset:  IM    
Center for Human Nutrition, Veterans Administration Medical Center, Omaha, Nebraska.
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MeSH Terms
Animals, Newborn
Asialoglycoprotein Receptor
Asialoglycoproteins / metabolism*
Cells, Cultured
Colchicine / pharmacology
Liver / growth & development*,  metabolism,  ultrastructure
Microtubules / drug effects,  metabolism*
Orosomucoid / analogs & derivatives*,  metabolism
Rats, Inbred Strains
Receptors, Immunologic / metabolism*
Reg. No./Substance:
0/Asialoglycoprotein Receptor; 0/Asialoglycoproteins; 0/Orosomucoid; 0/Receptors, Immunologic; 0/asialoorosomucoid; 64-86-8/Colchicine

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