AJP - Gastrointestinal and Liver Physiology, Vol 258, Issue 1 129-G137, Copyright © 1990 by American Physiological Society
Altered role of microtubules in asialoglycoprotein trafficking in developing liver
S. S. Kaufman, P. L. Blain, J. H. Park and D. J. Tuma
Center for Human Nutrition, Veterans Administration Medical Center, Omaha, Nebraska.
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.
