Alteration in the regulation of plasma membrane glycoproteins of the hepatocyte during ontogeny.
The expression of four integral membrane glycoproteins was examined in detail utilizing monospecific antibodies during liver development. These included asialoglycoprotein receptor, a hepatocyte glycoprotein residing in the sinusoidal domain, and three bile canalicular glycoproteins, leucine aminopeptidase, dipeptidyl peptidase IV, and a Mr 110,000 glycoprotein denoted GP 110. It was observed that asialoglycoprotein receptor, GP 110, and dipeptidyl peptidase IV were present in low amounts in fetal liver and reached adult levels between 1 to 3 weeks. In contrast, leucine aminopeptidase was present in nearly adult amounts in 18-day-old fetal livers. These observations were qualitatively confirmed by indirect immunofluorescent staining of frozen thin liver sections obtained from fetal and adult rats. Further, in fetal livers it was found that leucine aminopeptidase was not localized to typical bile canalicular areas. Immunoprecipitation studies performed in the presence of proteolytic inhibitors using detergent-solubilized extracts of metabolically labeled liver minces revealed that GP 110 was present in low amounts as Mr 110,000 and Mr 105,000 polypeptides in 17-day fetal livers but by 21 days of gestation the larger polypeptide was the major synthesis product. Conversely, the apparent molecular weights of leucine aminopeptidase and dipeptidyl peptidase IV were not altered during development. Experiments determining relative rates of synthesis using excess amounts of antibodies showed that the concentrations of the three bile canalicular glycoproteins in liver during ontogeny reflect their rates of synthesis. These results underscore that plasma membrane constituents of the hepatocyte undergo dramatic changes in expression and localization as the liver changes its physiological role at birth.
Petell
J K
JK
Colucci Memorial Liver Research Center, Children's Hospital, Buffalo, New York.
Quaroni
A
A
Hong
W J
WJ
Hixson
D C
DC
Amarri
S
S
Reif
S
S
Bujanover
Y
Y
D000375:Aging; D000818:Animals; D000911:Antibodies, Monoclonal; D037263:Asialoglycoprotein Receptor; D002462:Cell Membrane / Q000648:ultrastructure; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000032:analysis; D005333:Fetus; D005455:Fluorescent Antibody Technique; D006706:Homeostasis; D007106:Immune Sera; D007074:Immunoglobulin G; D007931:Leucyl Aminopeptidase / Q000032:analysis; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D008970:Molecular Weight; D051381:Rats; D011915:Rats, Inbred BUF; D011971:Receptors, Immunologic / Q000032:analysis
D000911:Antibodies, Monoclonal; D037263:Asialoglycoprotein Receptor; D007106:Immune Sera; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D007931:Leucyl Aminopeptidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4