AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 4 639-G645, Copyright © 1990 by American Physiological Society
Role of microfilaments in asialoglycoprotein processing in adult and 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.
To assess the role of microfilaments in receptor-mediated endocytosis of
asialoglycoproteins, hepatocytes isolated from adult and 6-day-old rats
were treated with the antimicrofilamentous agent cytochalasin D and then
incubated with 125I-asialoorosomucoid (ASOR). Cytochalasin D (50 microM)
reduced degradation of continuously endocytosed ASOR (7.5 micrograms/ml)
equally in adult and neonate to approximately 20% of control.
Internalization of surface-bound ASOR suggested at least two discrete sites
at which ligand translocation was inhibited by drug at both ages: 1)
initial movement of receptor-ligand complex from cell surface to interior
and 2) postinternalization ligand transit to lysosomes. Inhibition of
plasma membrane translocation was confirmed by calculation of endocytotic
rate constant (Ke) values, which were decreased to approximately 20-30% of
control after cytochalasin D treatment. In contrast, the antimicrotubular
drug colchicine did not reduce Ke values significantly nor did colchicine
in combination with cytochalasin D impede lysosome-directed transport more
than cytochalasin D alone. These results indicate that internalization of
occupied asialoglycoprotein surface receptor is microfilament dependent
irrespective of postnatal age and that subsequent participation of
microfilaments in asialoglycoprotein trafficking is closely related to that
of microtubules.
