N-cadherin mediates plasticity-induced long-term spine stabilization

Méndez, Pablo; Roo, Mathias De; Poglia, Lorenzo; Klauser, Paul; Michelet, Dominique

doi:10.1083/jcb.201003007

Cited by 133 publications

(120 citation statements)

References 33 publications

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“…On the other hand, in the rat RT4-D6P2T schwannoma cell line, UTP induces a transient elevation in concentrations of intracellular Ca 2+ and a subsequent cytoskeletal reorganisation [32]. In this context, N-cadherin, a member of the Ca 2+ -dependent CAM family, is related to multiple cytoskeletal elements and has an important role in SC migration, neurite outgrowth, synaptic rearrangement, creation of SC-SC junctions, and the alignment of SCs with axons [4,5,[33][34][35][36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

N-cadherin expression is regulated by UTP in schwannoma cells

Martiáñez

Lamarca

Casals

et al. 2012

Purinergic Signalling

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Schwann cells (SCs) are peripheral myelinating glial cells that express the neuronal Ca 2+ -dependent cell adhesion molecule, neural cadherin (N-cadherin). Ncadherin is involved in glia-glia and axon-glia interactions and participates in many key events, which range from the control of axonal growth and guidance to synapse formation and plasticity. Extracellular UTP activates P2Y purinergic receptors and exerts short-and long-term effects on several tissues to promote wound healing. Nevertheless, the contribution of P2Y receptors in peripheral nervous system functions is not completely understood. The current study demonstrated that UTP induced a dose-and timedependent increase in N-cadherin expression in SCs. Furthermore, N-cadherin expression was blocked by the P2 purinoceptor antagonist suramin. The increased N-cadherin expression induced by UTP was mediated by phosphorylation of mitogen-activated protein kinases (MAPKs), such as Jun N-terminal kinase, extracellular-regulated kinase and p38 kinase. Moreover, the Rho kinase inhibitor Y27632, the phospholipase C inhibitor U73122 and the protein kinase C inhibitor calphostin C attenuated the UTP-induced activation of MAPKs significantly. Extracellular UTP also modulated increased in the expression of the early transcription factors c-Fos and c-Jun. We also demonstrated that the region of the N-cadherin promoter between nucleotide positions −3698 and −2620, which contained one activator protein-1-binding site, was necessary for UTP-induced gene expression. These results suggest a novel role for P2Y purinergic receptors in the regulation of N-cadherin expression in SCs.

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Section: Discussionmentioning

confidence: 99%

N-cadherin expression is regulated by UTP in schwannoma cells

Martiáñez

Lamarca

Casals

et al. 2012

Purinergic Signalling

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“…Previous work has suggested that adhesion molecules, by increasing transsynaptic cohesion via N-cadherin [52] or PAP-synapse sticking through EphA4/ephrin-A3 contacts [17,53], could play a role in activity-dependent synapse stability. Here, we propose that PAPs could promote structural interactions and molecular communication between synaptic partners through their reduced motility and increased coverage of the synapse.…”

Section: Discussionmentioning

confidence: 99%

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

et al. 2014

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SummaryBackground: Excitatory synapses in the CNS are highly dynamic structures that can show activity-dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca 2+ elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca 2+ events in astrocytes and PAP morphological dynamics remain unclear. Results: In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability. Conclusions: This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.

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“…Several adhesion molecule systems have also been linked to spine stability, including neuroligin 1 (REFS 29,30) and N-cadherin. Activity-mediated expression of N-cadherin correlates with, and is required for, the long-term stabilization of spines activated by theta-burst stimulation 31 . Secreted members of the C1q family have also been shown to rapidly induce changes in synapse numbers by, for example, stabilizing synapses in the mature cerebellum in vivo through the formation of trans-synaptic complexes 32 .…”

Section: Spine Dynamicsmentioning

confidence: 99%

Structural plasticity upon learning: regulation and functions

2012

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The contributions of brain networks to information processing and learning and memory are classically interpreted within the framework of Hebbian plasticity and the notion that synaptic weights can be modified by specific patterns of activity. However, accumulating evidence over the past decade indicates that synaptic networks are also structurally plastic, and that connectivity is remodelled throughout life, through mechanisms of synapse formation, stabilization and elimination 1. This has led to the concept of structural plasticity, which can encompass a variety of morphological changes that have functional consequences. These include on the one hand structural rearrangements at pre-existing synapses, and on the other hand the formation or loss of synapses, of neuronal processes that form synapses or of neurons. In this Review we focus on plasticity that involves gains and/or losses of synapses. Its key potential implication for learning and memory is to physically alter circuit connectivity, thus providing long-lasting memory traces that can be recruited at subsequent retrieval. Detecting this form of plasticity and relating it to its possible functions poses unique challenges, which are in part due to our still limited understanding of how structure relates to function in the nervous system.We review recent studies that relate the structural plasticity of neuronal circuits to behavioural learning and memory and discuss conceptual and mechanistic advances, as well as future challenges. The studies establish a number of strong links between specific behavioural learning processes and the assembly and loss of specific synapses. Further areas of substantial progress include molecular and cellular mechanisms that regulate synapse dynamics in response to alterations in synaptic activity, the specific spatial distribution of the syn aptic changes among identified neurons and dendrites and the relative roles of excitation and inhibition in regulating structural plasticity.The new findings provide exciting early vistas of how learning and memory may be implemented at the level of structural circuit plasticity. At the same time, they highlight major gaps in our understanding of plasticity regulation at the cellular, circuit and systems levels. Accordingly, achieving a better mechanistic understanding of learning and memory processes is likely to depend on the development of more effective techniques and models to investigate ensembles of identified synapses longitudinally, both functionally and structurally. Molecular mechanisms of synapse remodellingA remarkable feature of excitatory and inhibitory synapses is their high level of structural variability 2 and the fact that their morphologies and stabilities change over time 3 . This phenomenon is regulated by activity, and the size of spine heads correlates with synaptic strength 4 , presynaptic properties 5 and the long-term stability of the synapse 6 . The morphological characteristics of synapses thus reveal important features of their function and stabilit...

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N-cadherin mediates plasticity-induced long-term spine stabilization

Abstract: Synaptic persistence is enhanced by N-cadherin, which clusters together in response to neural activity and long-term potentiation induction in dendritic spines.

Cited by 133 publications

References 33 publications

N-cadherin expression is regulated by UTP in schwannoma cells

N-cadherin expression is regulated by UTP in schwannoma cells

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

Structural plasticity upon learning: regulation and functions

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