Cadherin-catenin complex in learning and memory

Long-term potentiation (LTP), thought to be the cellular basis for learning and memory, involves a specific signal transmission process that underlies synaptic plasticity. Among the many mechanisms responsible for the maintenance of synaptic plasticity is the cadherin–catenin complex. By forming complexes with intracellular catenin proteins, neural cadherins (N-cadherins) serve as a link between synaptic activity and synaptic plasticity, and play important roles in the processes of learning and memory.

N-cadherins are believed to be involved in mediating LTP and the synaptic changes underlying learning and memory. During embryonic development, cadherins are initially widely distributed, but they become gradually more localized to pre- and post-synaptic sites while synapses are being formed. Blocking cadherin function with specific proteins does not affect basal synaptic properties, but it can impair the induction of LTP.

N-cadherins are transmembrane proteins expressed in the majority of CNS synapses. N-cadherins are most commonly expressed on both the presynaptic active zone and postsynaptic density (PSD) regions, and contain both extracellular Ca2+ binding domains as well as intracellular domains for binding their protein partners. A common binding partner for Cadherins are intracellular catenin proteins, specifically the three different subtypes, α-catenins, β-catenins, and p120ctn family catenins. β-catenins and p120ctns bind cadherin’s intracellular domain at the distal and proximal regions respectively. α-catenins, when in monomeric form, will associate with the cadherin-catenin complex via β-catenins. In homodimeric form, α-catenins do not bind β- catenins, but preferentially bind F-actin and other proteins promoting F-actin polymerization. Each catenin subtype and its interaction with cadherins plays a distinct role in the mediation of synaptic plasticity and spine structure.

Evidence suggest that N-Cadherins stabilize the connection between the presynaptic terminal and postsynaptic spine and that this stabilization increases the likelihood that released glutamate will bind receptors on the postsynaptic neuron. At basal levels of synaptic activity, N-cadherins are largely monomers and are thus weakly adhesive to cadherins located in the cell on the opposite side of the synapse. The influx of Ca2+ through NMDARs, promotes the dimerization of N-cadherins. Dimerized cadherins readily bind to their presynaptic cadherin partners. Inhibition of N-cadherin binding via blocking antibodies prevents the induction of late phase L-long term potentiation, suggesting that the adhesive property of dimeric N-cadherin is necessary for late phase L-LTP. Additionally, KCl depolarization of the presynaptic axon both confers protease resistance to N-cadherins and disperses them throughout the PSD from their original clustering in synaptic puncta, thus increasing their efficacy for cell adhesion.

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