Association of the gene encoding neurogranin with schizophrenia in males

Ruano, Dina; Aulchenko, Yurii S.; Macedo, António; Soares, M.J.; Valente, J.; Azevedo, M.H.; Hutz, Mara H.; Gama, Clarissa Severino; Lobato, Maria Inês Rodrigues; Belmonte-de-Abreu, Paulo; Goodman, Ann B.; Pato, Carlos N.; Heutink, Peter; Palha, Joana Almeida

doi:10.1016/j.jpsychires.2006.10.008

Cited by 45 publications

(39 citation statements)

References 74 publications

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“…Neurogranin is also a postsynaptic PKC substrate [89], regulates synaptic plasticity [90], and is implicated in schizophrenia [91,92]. In both AMPH and PSD models, along with imipramine treated rats, phosphorylation of neurogranin was increased [47].…”

Section: Downstream Targets Of Pkcmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.

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Section: Downstream Targets Of Pkcmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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“…The main function of neurogranin may be to act as a CaM reservoir, regulating its availability in the postsynaptic compartment. Altered neurogranin activity has been suggested to mediate the effects of NMDA hypofunction implicated in the pathophysiology of schizophrenia (43)(44)(45). Interestingly, this neurogranin C-terminal fragment KGPGPGGPGGAGGARGGAGGGPSGD contains 15 gly- Glycine-rich domains of proteins are involved in many different functional activities.…”

Section: Discussionmentioning

confidence: 99%

Similar Intracellular Peptide Profile of TAP1/β2 Microglobulin Double-Knockout Mice and C57BL/6 Wild-Type Mice as Revealed by Peptidomic Analysis

Castro

Berti²,

Russo³

et al. 2010

AAPS J

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Abstract. Cells produce and use peptides in distinctive ways. In the present report, using isotope labeling plus semi-quantitative mass spectrometry, we evaluated the intracellular peptide profile of TAP1/β2m −/− (transporter associated with antigen-processing 1/ß2 microglobulin) double-knockout mice and compared it with that of C57BL/6 wild-type animals. Overall, 92 distinctive peptides were identified, and most were shown to have a similar concentration in both mouse strains. However, some peptides showed a modest increase or decrease (~2-fold), whereas a glycine-rich peptide derived from the C-terminal of neurogranin (KGPGPGGPGGAGGARGGAGGGPSGD) showed a substantial increase (6-fold) in TAP1/β2m −/− mice. Thus, TAP1 and β2microglobulin have a small influence on the peptide profile of neuronal tissue, suggesting that the presence of peptides derived from intracellular proteins in neuronal tissue is not associated with antigens of the class I major histocompatibility complex. Therefore, it is possible that these intracellular peptides play a physiological role.

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“…None of them maps to the coding region of the gene. The SNP rs7113041 is located near the TRE localized at the first intron and was found in a male Portuguese population (110). On the other hand, the SNP rs12807809 is located 3,457 bases upstream of the translation initiation and was identified more recently in a study which combined SNP data from several large genome-wide scans (111).…”

Section: Pathologies and Future Perspectivesmentioning

confidence: 99%

Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

2010

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SummaryNeurogranin (Ng) (also named RC3, p17 or BICKS) is a small protein originally identified in rat brain and abundantly expressed in several telencephalic areas, such as the cerebral cortex, hippocampus, amygdala, and striatum. In neurons, it is found concentrated at dendritic spines where it participates in synaptic signaling events through the regulation of calmodulin (CaM) availability. Ng features an IQ motif that mediates its interaction with CaM and phosphatidic acid (PA) and that is phosphorylated by protein kinase C (PKC) at serine 36 (Ser36). Ser36-phosphorylated Ng is unable to bind either CaM or PA. Ng knockout mice display an apparently normal phenotype; however, they show severe deficits in spatial and emotional learning and a decrease in LTP induction, mostly due to the attenuation of the signaling that depends on calcium/CaM kinase II (CaMKII), PKC, and protein kinase A (PKA) activation. The present review is an update on the most relevant information about Ng expression, localization, interactions, and modifications as well as on its role in synaptic plasticity. IUBMBIUBMB Life, 62(8): 597-606, 2010

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Association of the gene encoding neurogranin with schizophrenia in males

Cited by 45 publications

References 74 publications

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Similar Intracellular Peptide Profile of TAP1/β2 Microglobulin Double-Knockout Mice and C57BL/6 Wild-Type Mice as Revealed by Peptidomic Analysis

Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

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