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

• Published in: Brain research Vol. 811; no. 1; pp. 29 - 33
• Main Authors: Hoffman, Keith B, Martinez, Julian, Lynch, Gary
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 16.11.1998; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Cell Adhesion Molecules - metabolism; Central nervous system; Extracellular matrix; Fundamental and applied biological sciences. Psychology; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hydrolysis; In Vitro Techniques; Long-Term Potentiation - physiology; LTP; Rats; Serine Endopeptidases - metabolism; Sulfones - pharmacology; Tissue plasminogen activator; Tissue Plasminogen Activator - metabolism; Trypsin Inhibitors - pharmacology; Vertebrates: nervous system and sense organs; Extracellular matrix; LTP; Tissue plasminogen activator; Hippocampus; Potentiation; Rat; Serine endopeptidases; Enzyme; Rodentia; Central nervous system; Cell adhesion molecule; Long term; t-Plasminogen activator; Peptidases; Vertebrata; Mammalia; Synaptic transmission; Proteolysis; Hydrolases; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• 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 μM. 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.