A role for the cadherin family of cell adhesion molecules in hippocampal long-term potentiation.
The cadherins are a family of cell-cell adhesion molecules that mediate Ca2+-dependent homophilic interactions between cells and transduce signals by interacting with cytoplasmic proteins. In the hippocampus, immunostaining combined with confocal microscopy revealed that both neural- (N-) and epithelial- (E-) cadherin are present at synaptic sites, implying a role in synaptic function. Pretreatment of hippocampal slices with antibodies (Abs) raised against the extracellular domain of either N-cad or E-cad had no effect on basal synaptic properties but significantly reduced long-term potentiation (LTP). Infusion of antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for cadherin dimerization also attenuated LTP induction without affecting previously established LTP. Because the intense synaptic stimulation associated with LTP induction might transiently deplete extracellular Ca2+ and hence potentially destabilize cadherin-cadherin interactions, we examined whether slices could be protected from inhibition by N-cad Abs or HAV peptides by raising the extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+ prevented the block of LTP by these agents. Taken together, these results indicate that cadherins are involved in synaptic plasticity, and the stability of cadherin-cadherin bonds may be regulated by synaptic stimulation.
Tang
L
L
Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Hung
C P
CP
Schuman
E M
EM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002645:Chickens; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry* / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D010446:Peptide Fragments / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000737:chemistry / Q000502:physiology
D000906:Antibodies; D015820:Cadherins; D010446:Peptide Fragments; D002118:Calcium