site, causing the β-catenin–cadherin complex to dissolve and consequently increasing synaptic vesicle mobility. Catenins also bind many scaffolding proteins, receptors, kinases and phosphatases. For example, the cadherin-α-catenin complex binds the actin cytoskeleton, though whether it binds via binding proteins or direct interactions is unknown. Signal transduction pathways p120ctn signals through guanine nucleotide exchange factors (GEFs) and GAPs to activate the Rho family of GTPases. RhoA must be inhibited by P120ctn to maintain spine density and length. Rac (GTPase) inhibition remediates a reduction of spine density in p120ctn deficiency. E-cadherin binding to p120ctn may activate SRC leading to activation of Rac1 which results in phosphorylation of LIMK1 and LIMK2 to deactivate cofilin causing G-actin polymerization. Meanwhile, phosphorylation of PI3K by SRC activates RhoA which leads to activation of cofilin-P and disruption of filamentous actin. When the WAVE-1 gene was disrupted in mice, it resulted in cognitive defects such as losses in learning and memory implicating the WAVE-1 branch of the Rac pathway. Using an in vivo dentate gyrus LTP model, it was shown that LTP induction is associated with an increase in F-actin in the dendritic spines, and this is a long lasting change. It was shown that NMDA receptor activation is required for this effect. Furthermore, the use of latrunculin A was able to impair late phase LTP in this model, again suggesting that actin remodelling is necessary for LTP. Cellular function Role in receptor trafficking/stability When the glutamate receptor binding protein ABP and p120ctn are co-expressed, anti-p120ctn serum pulls out a complex containing both proteins from cell lysates. The same occurs for a protein similar to ABP, called GRIP. cDNA screening and yeast mating assays demonstrate that the PDZ domain-binding motif at the p120ctn C-terminus enables such interactions. Co-IP data shows that p120ctn can simultaneously complex with cadherin and either ABP or GRIP. Dominant negative p120ctn fragments, which failed to interact with ABP and GRIP, impaired the stabilization of GluR2 and GluR3 AMPAR subunits, respectively, at the plasma membrane. Co-localization of p120ctn with PSD-95 suggests that cadherin-p120ctn-ABP/GRIP complexes anchor AMPARs at the postsynaptic density, but it is unclear whether anchoring also occurs at perisynaptic sites. Regulation of gene expression Cadherins and catenins have been shown to be involved in regulating gene expression, an important process in synaptic plasticity. Glutamate binding to NMDA upregulates the production of N-cadherin’s intracellular domain peptide, N-cad/CTF2, an effect blocked by the NMDA receptor antagonist,