Association of PSD‐95 with ErbB4 facilitates neuregulin signaling in cerebellar granule neurons in culture

Xie, Fang; Padival, Mallika; Siegel, Ruth E.

doi:10.1111/j.1471-4159.2006.04182.x

Cited by 20 publications

(17 citation statements)

References 45 publications

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“…For example, Rack1 is dissociated from the C-termini of NR2 subunits via activated PKA, permitting phosphorylation by Fyn and other Srk family kinases in a PSD-95-dependent manner (Cheng et al, 2008;Thornton et al, 2004;Yaka et al, 2002). Cdk5 can modulate Reelin and PSD-95/Fyn interactions (Beffert et al, 2004;Hawasli et al, 2007;Morabito et al, 2004;Ohshima et al, 2007;Xie et al, 2007a;Zhang et al, 2008). Thus, increased expression of Rack1, Cdk5, and Fyn suggests altered modulation of NMDAR-PSD-95 interactions at synaptic sites (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia

Funk

McCullumsmith

Haroutunian

et al. 2011

Neuropsychopharmacol

132

102

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Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3 0 -5 0 -cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK-and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC ¼ 36, DLPFC ¼ 35) and a comparison (ACC ¼ 33, DLPFC ¼ 31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK-and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK-and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK-and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia

Funk

McCullumsmith

Haroutunian

et al. 2011

Neuropsychopharmacol

132

102

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“…Mouse cerebellar neurons were cultured using a modification of a previously described procedure (63). In brief, cerebella were removed from 6-to 8-d-old mice.…”

Section: Methodsmentioning

confidence: 99%

Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner

Zhou

Hinman

Barron

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

129

139

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Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes. In both primary and mouse embryonic stem cell-derived neurons, histone hyperacetylation leads to an increased local transcriptional elongation rate and decreased inclusion of these exons. Furthermore, we demonstrate that Hu proteins interact with histone deacetylase 2 and inhibit its deacetylation activity. We propose that splicing regulators may actively modulate chromatin structure when recruited to their target RNA sequences cotranscriptionally. This "reaching back" interaction with chromatin provides a means to ensure accurate and efficient regulation of alternative splicing.histone acetylation | neurofibromatosis type 1 | Fas R ecent genome-wide transcriptome analysis has demonstrated that more than 95% of human genes undergo alternative splicing to produce multiple proteins from one gene (1-4). Most of these alternative splicing events lead to coding differences and occur in a cell type-and/or developmental stage-specific manner (3, 5), underscoring the essential role of alternative splicing in gene expression control. In addition to the well-established role of RNA-binding proteins in the regulation of pre-mRNA alternative splicing (6, 7), recent studies have revealed a role for chromatin-associated proteins and the transcription machinery in splicing regulation (8)(9)(10).A recent study of large human genes demonstrated that premRNA splicing is cotranscriptional and occurs within 5-10 min of synthesis (11). The tight coupling of transcription and splicing predicts cross-talk between chromatin structure and splicing regulation. Indeed, several recent studies have documented a number of interesting links between chromatin features and exon behavior. First, a ChIP analysis indicated that a specific histone modification, trimethylation of lysine 36 of histone H3 (H3K36me3), differentially marks exons (12, 13). Remarkably, this histone mark appears to be associated more significantly with constitutive exons than with alternative exons (13). Second, a genome-wide analysis of nucleosome occupancy showed that nucleosomes are enriched in exons and are depleted in introns, suggesting that nucleosome position helps to distinguish introns from exons (12,(14)(15)(16)(17). Although these studies provide significant evidence for cross-talk between chromatin and splicing, the nature of the cross-talk remains largely unknown. Several studies support a model in which histone marks function to recruit basal spliceosomal factors or splicing regulators to ensure efficient splicing regulation. For example, the histone mark H3K4m...

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“…Depolarization of cultured granule cells has thus been proposed to mimic the activity-dependent maturation of granule cells by mossy fiber input (Gallo et al, 1987) and is often used as a model system to explore regulatory mechanisms of granule cell maturation (Gu et al, 2007;Xie et al, 2007;Leó n et al, 2008;Mundy et al, 2008). However, the use of chronic high KCl has been questioned.…”

Section: Introductionmentioning

confidence: 99%

Role of Calcineurin Signaling in Membrane Potential-Regulated Maturation of Cerebellar Granule Cells

Okazawa

Abe²,

Katsukawa³

et al. 2009

J. Neurosci.

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Association of PSD‐95 with ErbB4 facilitates neuregulin signaling in cerebellar granule neurons in culture

Cited by 20 publications

References 45 publications

Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia

Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia

Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner

Role of Calcineurin Signaling in Membrane Potential-Regulated Maturation of Cerebellar Granule Cells

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