Regulation of asialoglycoprotein receptor activity by a novel inactivation/reactivation cycle. Receptor reactivation in permeable rat hepatocytes is mediated by fatty acyl coenzyme A.

摘要: We previously reported that a subpopulation of asialoglycoprotein receptors (ASGP-Rs), designated State 2 ASGP-Rs, can be inactivated in digitonin-permeabilized hepatocytes the absence cytosol by process is temperature- and ATP-dependent (Medh, J. D., Weigel, P. H. (1991) Biol. Chem. 266, 8771-8778). Here we show these ASGP-Rs are reactivated sole addition fatty acyl-CoA. Of derivatives tested (acyl chain length 4-18), palmitoyl-CoA was most effective, although stearoyl-CoA (C18) myristoyl-CoA (C14) were also active. Lauroyl-CoA (C12) about half as effective palmitoyl-CoA, decanoyl-CoA (C10) butyl-CoA (C4) inactive. ASGP-R reactivation did not take place presence free palmitate coenzyme A, but occur if low levels ATP added to drive synthesis permeable cells. Addition after with again resulted rapid inactivation receptors. The extent rate this second proportional concentration; half-maximal effects occurred at approximately 0.5 mM ATP. rapidly reversed seen other acyl-CoAs. results demonstrate existence unrecognized pathway regulates activity population responsible for majority ligand endocytosis processing hepatocytes. This novel receptor inactivation/reaction cycle could ensure high efficiency segregating during recycling.