Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of schizophrenia and bipolar disorder patients

Torres, Karen; Souza, Bruno R.; Miranda, Débora Marques de; Sampaio, André M.; Nicolato, Rodrigo; Neves, Fernando Silva; Barros, A.G.A.; Dutra, Walderez O.; Gollob, Kenneth J.; Corrêa, Humberto; Romano-Silva, Marco Aurélio

doi:10.1016/j.pnpbp.2008.11.011

Cited by 32 publications

(22 citation statements)

References 42 publications

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“…No human study has measured gammaband activity and correlated it with NCS-1 levels. Unfortunately, serum sampling does not reflect brain levels and, in fact, NCS-1 levels in leukocytes are actually decreased in schizophrenic patients (Torres et al 2009). However, future clinical trials in patients with schizophrenia or bipolar disorder may benefit from prior determination of a significant decrease in gamma-band activity, which may also help address the heterogeneity of schizophrenia and facilitate the process of identifying more homogeneous groups within the syndrome (Picardi et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder

D’Onofrio

Kezunovic

Hyde

et al. 2015

Journal of Neurophysiology

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D'Onofrio S, Kezunovic N, Hyde JR, Luster B, Messias E, Urbano FJ, Garcia-Rill E. Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder. J Neurophysiol 113: 709 -719, 2015. First published November 5, 2014 doi:10.1152/jn.00828.2014.-Reduced levels of gamma-band activity are present in schizophrenia and bipolar disorder patients. In the same disorders, increased neuronal calcium sensor protein-1 (NCS-1) expression was reported in a series of postmortem studies. These disorders are also characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). The discovery of gamma-band activity in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, revealed that such activity was mediated by high-threshold calcium channels that are regulated by NCS-1. We hypothesized that NCS-1 normally regulates gamma-band oscillations through these calcium channels and that excessive levels of NCS-1, such as would be expected with overexpression, decrease gammaband activity. We found that PPN neurons in rat brain slices manifested gamma-band oscillations that were increased by low levels of NCS-1 but suppressed by high levels of NCS-1. Our results suggest that NCS-1 overexpression may be responsible for the decrease in gamma-band activity present in at least some schizophrenia and bipolar disorder patients.

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Section: Discussionmentioning

confidence: 99%

Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder

D’Onofrio

Kezunovic

Hyde

et al. 2015

Journal of Neurophysiology

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“…Human interleukin-1 receptor accessory protein-like (IL1RAPL1) interacts with NCS-1, and both proteins are involved in X-linked mental retardation and autism (Bahi et al, 2003;Pavlowsky et al, 2010). Furthermore, a missense (R102Q) mutation in NCS-1 has been reported in one case of autism (Piton et al, 2008), and schizophrenic and bipolar disorder patients show an excess of NCS-1 in their dorsolateral prefrontal cortex (Koh et al, 2003) and a decrease of the protein in leukocytes (Torres et al, 2009). In view of the large repertoire of functional interactions reported so far, the search for unifying mechanisms that could account for the biology of this Ca 2+ sensor is justified.…”

Section: Introductionmentioning

confidence: 99%

The guanine-exchange factor Ric8a binds the calcium sensor NCS-1 to regulate synapse number and probability of release

Romero-Pozuelo

Dason

Mansilla

et al. 2014

Journal of Cell Science

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The conserved Ca 2+ -binding protein Frequenin (homolog of the mammalian NCS-1, neural calcium sensor) is involved in pathologies that result from abnormal synapse number and probability of neurotransmitter release per synapse. Both synaptic features are likely to be co-regulated but the intervening mechanisms remain poorly understood. We show here that Drosophila Ric8a (a homolog of mammalian synembryn, which is also known as Ric8a), a receptor-independent activator of G protein complexes, binds to Frq2 but not to the virtually identical homolog Frq1. Based on crystallographic data on Frq2 and site-directed mutagenesis on Frq1, the differential amino acids R94 and T138 account for this specificity. Human NCS-1 and Ric8a reproduce the binding and maintain the structural requirements at these key positions. Drosophila Ric8a and Gas regulate synapse number and neurotransmitter release, and both are functionally linked to Frq2. Frq2 negatively regulates Ric8a to control synapse number. However, the regulation of neurotransmitter release by Ric8a is independent of Frq2 binding. Thus, the antagonistic regulation of these two synaptic properties shares a common pathway, Frq2-Ric8a-Gas, which diverges downstream. These mechanisms expose the Frq2-Ric8a interacting surface as a potential pharmacological target for NCS-1-related diseases and provide key data towards the corresponding drug design.

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“…Moreover NCS-1 expression in C. elegans controls learning and memory (Gomez et al 2001). In patients with schizophrenia or bipolar disorders, NCS-1 level is upregulated in the prefrontal cortex (Koh et al 2003) and decreased in leukocytes as been shown recently (Torres et al 2009). NCS-1 interacts with many proteins, some in calcium dependent and some in calcium independent ways like GRK2 (G-protein-coupled receptor kinase2) (Sallese et al 2000), D2 Dopamine receptor (Kabbani et al 2002), IL1RAPL (interleukin-1 receptor accessory protein-like protein) (Bahi et al 2003), ARF1 (ADP Ribosylation factor) (Haynes et al 2005), IP3-receptor (Schlecker et al 2006), Nitric oxide synthase etc.…”

mentioning

confidence: 74%

Resonance assignments of myristoylated and non-myristoylated neuronal calcium sensor-1(NCS-1) embedded in a membrane

et al. 2010

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Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of schizophrenia and bipolar disorder patients

Cited by 32 publications

References 42 publications

Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder

Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder

The guanine-exchange factor Ric8a binds the calcium sensor NCS-1 to regulate synapse number and probability of release

Resonance assignments of myristoylated and non-myristoylated neuronal calcium sensor-1(NCS-1) embedded in a membrane

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