Receptor-mediated endocytosis and degradation of insulin-like growth factor I and II in neonatal rat astrocytes

J Neurosci Res. 1992 Jan;31(1):14-20. doi: 10.1002/jnr.490310103.


Receptor-mediated internalization and degradation of insulin-like growth factors, IGF-I and IGF-II, were studied in primary cultures of neonatal rat astrocytes. Surface-bound IGF-II was rapidly internalized, and 80% of cell-associated radioactivity was located intracellularly after 30 min. IGF-I was internalized at a slower rate, and only 40% of cell-associated radioactivity was inside the cell after 30 min. A pulse-chase experiment demonstrated that 55% and 70% of internalized IGF-I and IGF-II, respectively, was degraded to free amino acids after a 3-hr chase. Lysosomal and protease inhibitors had different effects on the binding, internalization, and processing of IGF-I and IGF-II. Inhibition of lysosomal acidification by chloroquine increased the amounts of surface-bound IGF-II and intracellular IGF-I and reduced the degradation of IGF-I. The chelating agent phenanthroline increased the surface binding of IGF-I and IGF-II and internalization of IGF-II and reduced the degradation of IGF-I and IGF-II. Finally, receptor-bound IGF-II on the cell surface was decreased with increasing cell density, whereas IGF-I binding was unaltered. Our data suggest that cell-surface expression of IGF-I receptors and IGF-II receptors is regulated by different mechanisms and that receptor-bound IGF-I and IGF-II are trafficked and processed by different intracellular pathways in neonatal rat astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / metabolism*
  • Cell Count
  • Cells, Cultured
  • Chloroquine / pharmacology
  • Endocytosis*
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor II / metabolism*
  • Kinetics
  • Lysosomes / drug effects
  • Phenanthrolines / pharmacology
  • Protease Inhibitors / pharmacology
  • Rats
  • Receptor, IGF Type 2
  • Receptors, Cell Surface / metabolism*
  • Receptors, Somatomedin


  • Phenanthrolines
  • Protease Inhibitors
  • Receptor, IGF Type 2
  • Receptors, Cell Surface
  • Receptors, Somatomedin
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Chloroquine