A Role for the Cadherin Family of Cell Adhesion Molecules in Hippocampal Long-Term Potentiation

Abstract

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.

The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses

“…Evidence for the latter is provided by the observation that the disturbance of synaptic cell adhesion, e.g., in mutant animals or by the application of antibodies or competitive peptides, in many cases interferes with long-term changes of synaptic plasticity. This has been reported for Ig superfamily CAMs NCAM180 and L1 (15,16), telencephalin (17), Fasciclin 2 (18), and Aplysia apCAM (19), as well as for cadherins (20) and integrins (21,22).…”

Cadherins and synaptic plasticity: activity-dependent cyclin-dependent kinase 5 regulation of synaptic β-catenin-cadherin interactions

“…Several recent studies support a role for the classic cadherins in synaptic plasticity (Tang et al 1998;Benson & Tanaka 1998;Tanaka et al 2000;Bozdagi et al 2000). We previously reported (Tang et al 1998) that either cadherin function-blocking antibodies or inhibitory peptides blocked LTP in area CA1 of rat hippocampal slices.…”

“…Cadherins are a family of proteins that mediate Ca 2ϩ -dependent homophilic cell adhesion (Takeichi 1990). Cadherins are located at synaptic sites (Fannon & Colman 1996;Uchida et al 1996;Tang et al 1998) and biochemical studies have demonstrated that cadherins associate with core synaptic proteins both pre-and postsynaptically (Husi et al 2000;Phillips et al 2001), suggesting that cadherins regulate synaptic function.…”

“…We previously reported (Tang et al 1998) that either cadherin function-blocking antibodies or inhibitory peptides blocked LTP in area CA1 of rat hippocampal slices. Using a different stimulation protocol designed to elicit L-LTP, Benson and colleagues showed that an antibody to N-cadherin blocked early-phase but not L-LTP.…”

Regulation of AMPA receptors and synaptic plasticity

“…Recently, several reports have shown that N-cadherin and its cognate cytoplasmic interacting protein betacatenin regulate synaptic structure and functions in an activity-dependent manner (Murase et al, 2002;Togashi et al, 2002;Yu and Malenka, 2003). This is of a particular interest because N-cadherin has been shown to be modified by neuronal activity and to play important roles in synaptic plasticity (Tang et al, 1998;Bozdagi et al, 2000;Tanaka et al, 2000). N-cadherin associates and co-localizes with AMPARs in neurons, in a cis manner, and this association is regulated by the extracellular Ca 2ϩ concentration (Nuriya and Huganir, 2006).…”