Role of NCAM in Spine Dynamics and Synaptogenesis

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

doi:10.1007/s11064-008-9653-5

Cited by 11 publications

(6 citation statements)

References 66 publications

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“…Since PSA-NCAM is a major player in structural plastic processes such as neurite elongation, cell migration and synaptogenesis as well as synaptic remodelling (Muller et al, 2008 ;Rutishauser and Landmesser, 1996 ;Seki and Rutishauser, 1998), which are compromised in schizophrenia (Frost et al, 2004), we can hypothesize a beneficial effect of olanzapine on neuroplastic deficits in mPFC through changes in synaptic structure and connectivity, perhaps mediated by an increase of PSA-NCAM. Although we did not investigate the cellular phenotype of PSA-NCAM-expressing cells, it has recently been demonstrated that PSA-NCAM immunoreactive cells in the mPFC are probably GABAergic interneurons (Varea et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Olanzapine, but not haloperidol, enhances PSA-NCAM immunoreactivity in rat prefrontal cortex

Frasca

Fumagalli

Horst

et al. 2008

Int. J. Neuropsychopharm.

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Repeated antipsychotic treatment may produce adaptive changes ranging from cytoarchitectural rearrangements to synaptic modifications that might contribute to clinical improvement. We performed a prolonged treatment (2 wk) with the first-generation antipsychotic (FGA) haloperidol (1 mg/kg) and the second-generation antipsychotic (SGA) olanzapine (2 mg/kg twice daily) and analysed the expression of the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in rat hippocampus and prefrontal cortex via immunohistochemistry. We found a regional- and drug-selective increase of PSA-NCAM expression in prefrontal cortex of olanzapine-treated rats with no effects in hippocampus; conversely, haloperidol did not produce a change in either brain region. Our findings reveal a possible role for PSA-NCAM in the mechanism of action of the SGA olanzapine adding complexity as well as specificity to the molecular changes set in motion by this drug.

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Section: Discussionmentioning

confidence: 99%

Olanzapine, but not haloperidol, enhances PSA-NCAM immunoreactivity in rat prefrontal cortex

Frasca

Fumagalli

Horst

et al. 2008

Int. J. Neuropsychopharm.

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“…NCAM1 is one of the first molecules to accumulate at forming synapsis, promoting membrane binding between neurons and the stabilization of the connection. Indeed, the overexpression of the protein led to a stimulation of the formation of synapses while a deficiency results in a reduction in the total volume of dendritic spines [ 58 , 59 , 60 ]. NCAM1 is important not only for synapse formation but also for the regulation of synapse dynamics due to its interaction with different cytosolic (e.g., actin and microtubules cytoskeleton) and membrane components from the presynaptic and postsynaptic compartments [ 56 , 57 , 58 , 59 , 60 , 61 , 62 ].…”

Section: Introductionmentioning

confidence: 99%

The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions

Parcerisas

Ortega-Gascó

Pujadas

et al. 2021

IJMS

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Although it has been over 20 years since Neural Cell Adhesion Molecule 2 (NCAM2) was identified as the second member of the NCAM family with a high expression in the nervous system, the knowledge of NCAM2 is still eclipsed by NCAM1. The first studies with NCAM2 focused on the olfactory bulb, where this protein has a key role in axonal projection and axonal/dendritic compartmentalization. In contrast to NCAM1, NCAM2’s functions and partners in the brain during development and adulthood have remained largely unknown until not long ago. Recent studies have revealed the importance of NCAM2 in nervous system development. NCAM2 governs neuronal morphogenesis and axodendritic architecture, and controls important neuron-specific processes such as neuronal differentiation, synaptogenesis and memory formation. In the adult brain, NCAM2 is highly expressed in dendritic spines, and it regulates synaptic plasticity and learning processes. NCAM2’s functions are related to its ability to adapt to the external inputs of the cell and to modify the cytoskeleton accordingly. Different studies show that NCAM2 interacts with proteins involved in cytoskeleton stability and proteins that regulate calcium influx, which could also modify the cytoskeleton. In this review, we examine the evidence that points to NCAM2 as a crucial cytoskeleton regulation protein during brain development and adulthood. This key function of NCAM2 may offer promising new therapeutic approaches for the treatment of neurodevelopmental diseases and neurodegenerative disorders.

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“…NCAM180 and NCAM140 are transmembrane isoforms, while NCAM120 is attached to the membrane via a glycophosphatidylinositol anchor. Functional triggering of NCAM leads to neural cell migration, neurite outgrowth and fasciculation, synaptogenesis, synaptic plasticity, and certain forms of emotional behavior, thus most likely implicating different molecular mechanisms in signaling (for reviews, see Brennaman and Maness, 2010;Conboy et al, 2010;Ditlevsen and Kolkova, 2010;Muller et al, 2010). Homophilic or heterophilic interactions between NCAM and its extracellular binding partners, in particular with fibroblast growth factor (FGF) receptors (for review, see Kiselyov, 2010) and glial cell line-derived neurotrophic factor (GDNF) receptor (Paratcha et al, 2003), trigger NCAMdependent intracellular signaling events resulting in these distinct cellular responses.…”

Section: Introductionmentioning

confidence: 99%

NCAM-Induced Neurite Outgrowth Depends on Binding of Calmodulin to NCAM and on Nuclear Import of NCAM and fak Fragments

Kleene

Mzoughi²,

Joshi³

et al. 2010

J. Neurosci.

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The neural cell adhesion molecule NCAM plays important functional roles not only during nervous system development, but also in the adult after injury and in synaptic plasticity. Homophilic binding of NCAM triggers intracellular signaling events resulting in cellular responses such as neurite outgrowth that require NCAM palmitoylation-dependent raft localization and activation of the nonreceptor tyrosine kinases fyn and fak. In this study, we show that stimulation of NCAM by a function-triggering NCAM antibody results in proteolytic processing of NCAM and fak. The C-terminal fragment of NCAM, consisting of the intracellular domain, the transmembrane domain, and a stub of the extracellular domain, and the N-terminal fragment of fak are imported into the nucleus. NCAM-stimulated fak activation, generation, and nuclear import of NCAM and fak fragments as well as neurite outgrowth are abolished by mutation of the calmodulin binding motif in the intracellular domain of NCAM that is responsible for the calcium-dependent binding of calmodulin to NCAM. This mutation interferes neither with NCAM cell surface expression, palmitoylation, and raft localization nor with fyn activation. The way by which the transmembrane NCAM fragment reaches the nucleus in a calmodulin-and calcium-dependent manner is by endocytotic transport via the endoplasmic reticulum and the cytoplasm. The generation and nuclear import of NCAM and phosphorylated fak fragments resulting from NCAM stimulation may represent a signal pathway activating cellular responses in parallel or in association with classical kinase-and phosphorylation-dependent signaling cascades.

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Role of NCAM in Spine Dynamics and Synaptogenesis

Cited by 11 publications

References 66 publications

Olanzapine, but not haloperidol, enhances PSA-NCAM immunoreactivity in rat prefrontal cortex

Olanzapine, but not haloperidol, enhances PSA-NCAM immunoreactivity in rat prefrontal cortex

The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions

NCAM-Induced Neurite Outgrowth Depends on Binding of Calmodulin to NCAM and on Nuclear Import of NCAM and fak Fragments

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