Catenins: playing both sides of the synapse

Abstract

Synapses of the central nervous system (CNS) are specialized cell-cell junctions that mediate intercellular signal transmission from one neuron to another. The directional nature of signal relay requires that synaptic contacts are morphologically asymmetric with distinct protein components, while changes in synaptic communication during neural network formation require synapses to be plastic. Synapse morphology and plasticity require a dynamic actin cytoskeleton. Classical cadherins, which are junctional proteins associated with the actin cytoskeleton, localize to synapses and regulate synaptic adhesion, stability and remodeling. The major intracellular components of cadherin junctions are the catenin proteins, and increasing evidence suggests that cadherin-catenin complexes modulate an array of synaptic processes. Here we review the role of catenins in regulating the development of pre-and postsynaptic compartments and function in synaptic plasticity, with particular focus on their role in regulating the actin cytoskeleton.

Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of β-catenin in dopamine neurons

“…Previous studies have demonstrated that post-synaptic b-catenin deletion in cultured hippocampal neurons alters homeostatic adaptations at the presynaptic site (Vitureira et al 2011). Therefore, as it has previously been shown that the structure and function of presynaptic and post-synaptic components of the synapse are highly coordinated (Kwiatkowski et al 2007;Vitureira et al 2011), it is possible that expression of b-catenin at the presynaptic site, in DA axon terminals, is necessary to coordinate the formation and function of post-synaptic sites in striatal medium spiny neurons.…”

“…In addition to its role in development and cell proliferation, b-catenin has been implicated in neuronal synapse regulation and remodeling by acting both pre-and post-synaptically (Kwiatkowski et al 2007). For example, previous studies have shown that genetic deletion of the gene that encodes b-catenin, Ctnnb1, in the amygdala results in impaired learning by disrupting the consolidation of memories induced by fear (Maguschak and Ressler 2008).…”

“…This signaling pathway has recently been shown to be involved in the regulation of hippocampal long-term potentiation in slice preparations (Chen et al 2006). b-catenin is also present at preand post-synaptic terminals and its association with cadherins and the actin cytoskeleton within synaptic complexes suggests direct participation in synaptic remodeling (Kwiatkowski et al 2007). Schuman and Murase recently demonstrated that neuronal depolarization causes b-catenin to move from the dendritic shafts into spines where it interacts with cadherin to influence synaptic plasticity and strength (Murase et al 2002).…”

“…This capacity for change continues during adulthood and underlies the ability to learn and remember by encoding changes in the environment. In recent years, the intracellular signaling molecule, b-catenin has been demonstrated to play a critical role in both neural circuit formation and synaptic plasticity (Murase and Schuman 1999;Weis and Nelson 2006;Kwiatkowski et al 2007;Maguschak and Ressler 2012). As a key component of the Wnt signaling pathway, upon activation, b-catenin translocates to the nucleus where it binds the TCF/LEF family of transcription factors to regulate the expression of Wnt targeted genes.…”

Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia

“…Another rare nonsynonymous SNP was found in one patient and an affected sibling, but no other patients, so its significance could be not determined. Recently published studies suggest that genetic variation in the cadherin member FAT is involved in BD (Blair et al, 2006), and haplotypes within 22q11-linked ARVCF, a member of the catenin family that maps immediately 3' to COMT, are associated with SZ (Sanders et al, 2005); catenins interact with cadherins to modulate synaptic function (reviewed by Kwiatkowski et al, 2007).…”