A cycloheximide-resistant pool of receptors for asialoglycoproteins and mannose 6-phosphate residues in the Golgi complex of hepatocytes.
Following in vivo administration of cycloheximide (20 mg/kg body weight i.p.) protein synthesis was completely inhibited (99%) in rat liver. No newly synthesized asialoglycoprotein receptor (ASGP-R) could be detected by metabolic labeling. Fluorescence immunocytochemistry of several secretory proteins and plasma membrane proteins, including the receptors for polymeric IgA (IgA-R), demonstrated a rapid loss from the Golgi complex following cycloheximide administration. On the other hand, two membrane proteins, the receptors for ASGP-R and mannose 6-phosphate (MP-R), were not altered in their cellular localization including the Golgi. Using quantitative immunoelectron microscopy with colloidal gold, we found that 2 h and 4 h after cycloheximide administration, the densities of ASGP-R and MP-R in the membranes of the Golgi complex were unaltered compared with control liver. Similarly, there was no significant effect of cycloheximide on the receptor labeling in coated vesicles and compartment of uncoupling receptors and ligands (CURL). These observations are consistent with an involvement of the Golgi and CURL pools of the receptors in intracellular trafficking, endocytosis and receptor recycling.
D000818:Animals; D037263:Asialoglycoprotein Receptor; D003513:Cycloheximide / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006600:Hexosephosphates / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008360:Mannosephosphates / Q000378:metabolism*; D008854:Microscopy, Electron; D008970:Molecular Weight; D009961:Orosomucoid / Q000031:analogs & derivatives; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D006600:Hexosephosphates; D008360:Mannosephosphates; D009961:Orosomucoid; D011971:Receptors, Immunologic; C027693:mannose-6-phosphate; D003513:Cycloheximide