Proteolysis of cell adhesion molecules by serine proteases: a role in long term potentiation?

Brain Res. 1998 Nov 16;811(1-2):29-33. doi: 10.1016/s0006-8993(98)00906-8.


Tissue plasminogen activator (tPA), a serine protease endogenous to hippocampal neurons, is shown to recognize a highly conserved sequence in the extracellular domain of cell adhesion molecules (CAMs). When added to brain homogenates, tPA generated a CAM fragment similar in size to that produced in hippocampal slices by brief periods of NMDA receptor stimulation. The serine protease inhibitor 4-(2-Aminoethyl)-benzenesulfonyl fluoride blocked the effects of tPA with an approximately 50% suppression at 250 microM. The inhibitor at this concentration had no evident effect on synaptic responses but caused long term potentiation to decay back to baseline over a 1 h period. These results suggest that extracellular breakdown of cell adhesion molecules initiated by NMDA receptors and mediated by serine proteases contributes to the formation of stable potentiation.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hydrolysis
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Rats
  • Serine Endopeptidases / metabolism*
  • Sulfones / pharmacology
  • Tissue Plasminogen Activator / metabolism*
  • Trypsin Inhibitors / pharmacology


  • Cell Adhesion Molecules
  • Sulfones
  • Trypsin Inhibitors
  • 4-(2-aminoethyl)benzenesulfonylfluoride
  • Serine Endopeptidases
  • Tissue Plasminogen Activator