NMDA Receptor Stimulation and Brain-Derived Neurotrophic Factor Upregulate Homer 1a mRNA via the Mitogen-Activated Protein Kinase Cascade in Cultured Cerebellar Granule Cells

Sato, Masaaki; Suzuki, Kazunori; Nakanishi, Shigetada

doi:10.1523/jneurosci.21-11-03797.2001

Cited by 125 publications

(128 citation statements)

References 36 publications

(45 reference statements)

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“…The prominent and rapid appearance of the intron 1-specific signal documents that FISH visualizes primary transcripts. Thus, the activity-induced upregulation of Homer 1 RNA results from de novo synthesis, in keeping with its sensitivity to the RNA polymerase inhibitor actinomycin D (Sato et al, 2001). As expected, the signals specific for Homer 1 exon 1 and Homer 1 intron 1 as well as for exon 1 and Homer 1a 3Ј UTR were colocalized in nuclei (Fig.…”

Section: Fluorescent In Situ Hybridization Reveals New Primary Homer supporting

confidence: 82%

“…Detection of a MECS-induced intranuclear FISH signal with an intronic riboprobe indicates that the sharp increase in IEG transcripts results from increased transcriptional initiation rates and hence de novo RNA synthesis. Complementary results were obtained by glutamate stimulation of cultured cerebellar granule cells (Sato et al, 2001). The intronspecific signal, but not the exon-specific signals, decayed 30 min after MECS, consistent with primary transcript processing.…”

Section: Activity-induced Transcriptional Upregulation and Homer 1 Prsupporting

confidence: 74%

“…Thus, induced neuronal activity leads foremost to an increase in transcript levels for the IEG forms of Homer 1, in concordance with previous in situ hybridization data (Brakeman et al, 1997) and the notion that activity changes Homer protein function . This increase in Homer 1 IEG forms results from de novo synthesis, as reported in cultured cerebellar granule cells (Sato et al, 2001) and determined by in situ visualization of nuclear transcripts in the hippocampus (see below).…”

Section: Induced Neuronal Activity Boosts Homer 1a and Ania 3 Transcrmentioning

confidence: 59%

“…3). The presence of sites for the cAMP responsive elementbinding protein family of transcription factors is indeed expected from the involvement of the mitogen-activated protein kinase in Homer 1a induction (Sato et al, 2001). The Homer 1 promoter lacks the serum response element that is important for induction of c-fos by MAP kinase and p90 rsk (Edwards, 1994), but it contains instead a similar cis-element, termed MEF-2, that can be activated by serum (Y.…”

Section: Tata-less Promoter and Multiple Transcriptional Start Sitesmentioning

confidence: 99%

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Synaptic Activity-Induced Conversion of Intronic to Exonic Sequence in Homer 1 Immediate Early Gene Expression

et al. 2002

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Three Homer genes regulate the activity of metabotropic glutamate receptors mGluR1a and mGluR5 and their coupling to releasable intracellular Ca2+pools and ion channels. Only the Homer 1 gene evolved bimodal expression of constitutive (Homer 1b and c) and immediate early gene (IEG) products (Homer 1a and Ania 3). The IEG forms compete functionally with the constitutive Homer proteins. The complex expression of the Homer 1 gene, unique for IEGs, focused our attention on the gene organization. In contrast to most IEGs, which have genes that are <5 kb, the Homer 1 gene was found to span ∼100 kb. The constitutive Homer 1b/c forms are encoded by exons 1–10, whereas the IEG forms are encoded by exons 1–5 and parts of intron 5. RNase protection demonstrated a >10-fold activity-dependent increase in mRNA levels exclusively for the IEG forms. Moreover, fluorescentin situhybridization documented that new primary Homer 1 transcripts are induced in neuronal nuclei within a few minutes after seizure, typical of IEGs, and that Homer 1b-specific exons are excluded from the activity-induced transcripts. Thus, at the resting state of the neurons, the entire gene is constitutively transcribed at low levels to yield Homer 1b/c transcripts. Neuronal activity sharply increases the rate of transcription initiation, with most transcripts now ending within the central intron. These coordinate transcriptional events rapidly convert a constitutive gene to an IEG and regulate the expression of functionally different Homer 1 proteins.

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Section: Fluorescent In Situ Hybridization Reveals New Primary Homer supporting

confidence: 82%

Section: Activity-induced Transcriptional Upregulation and Homer 1 Prsupporting

confidence: 74%

Section: Induced Neuronal Activity Boosts Homer 1a and Ania 3 Transcrmentioning

confidence: 59%

Section: Tata-less Promoter and Multiple Transcriptional Start Sitesmentioning

confidence: 99%

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Synaptic Activity-Induced Conversion of Intronic to Exonic Sequence in Homer 1 Immediate Early Gene Expression

et al. 2002

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“…We previously found the down-regulation of the high-affinity BDNF receptor, TrkB, in corticolimbic regions of schizophrenic patients. As BDNF/TrkB signaling is a potent regulator for the expression of various PDZ protein (Jourdi et al 2001;Sato et al 2001), the impaired BDNF/TrkB signaling of schizophrenic patients might be responsible for the SAP97 protein decrease in the prefrontal cortex of schizophrenic patients. Interestingly, a major psychotomimetic drug, phencyclidine, acutely alters SAP97 gene expression, suggesting a potential link between psychotic symptoms and the PDZ protein SAP97 (Linden et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Toyooka

Iritani

Makifuchi

et al. 2002

Journal of Neurochemistry

111

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Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients. Keywords: chapsyn-110, GRIP1, PSD-95, psychosis, SAP102, SAP97. Address correspondence and reprint requests to Hiroyuki Nawa, Department of Molecular Biology, Brain Research Institute, Niigata University, Asahimachi-dori 1-757, Niigata 951-8585, Japan. E-mail: hnawa@bri.niigata-u.ac.jpAbbreviations used: ABP, AMPA receptor-binding protein; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid; BDNF, brainderived neurotrophic factor; DTT, dithiothreitol; LPT, long-term potentiation; NSE, neuron-specific enolase; PAGE, polyacrylamide gel electrophoresis; PDZ, PSD-95/discs large/zone occludens-1; PVDF, polyvinylidene difluoride; PSD, postsynaptic density; SAP, synapseassociated protein; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

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Differential expression of Homer family proteins in the developing mouse brain

Shiraishi¹,

Mizutani²,

Yuasa³

et al. 2004

J of Comparative Neurology

101

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Homer acts as a postsynaptic adaptor protein that links multiple targets, such as proteins involved in glutamate receptor signaling. We report the differential expression of the long form of Homer proteins produced from three distinctive genes during postnatal development of the mouse brain. Homer 1b/c and Cupidin/Homer 2a/b are widespread throughout the developing brain and are down-regulated in hindbrain-origin regions, such as the cerebellum, pons, and medulla oblongata. In contrast, Homer 3a/b is restricted to the cerebellum, hippocampus, and neonatal olfactory bulb. In the cerebellum, Homer 1b/c and Cupidin/Homer 2a/b predominate in the postsynapses of developing granule cells, whereas Homer 3a/b is concentrated in the dendritic spines of Purkinje cells and their axons. The down-regulation of Homer 1b/c and Cupidin/Homer 2a/b is in marked contrast to the up-regulation of Homer 3a/b between the first and the second postnatal weeks. In the hippocampus, Homer 1b/c and Cupidin/Homer 2a/b are largely located in the CA1 region and the CA1-CA2 region, respectively, whereas Homer 3a/b is largely distributed in the CA2-CA3 region and peaks around the third postnatal week. In hippocampal cell cultures, Homer 1b/c and Cupidin/Homer 2a/b are expressed in inhibitory and excitatory neurons, whereas Homer 3a/b is largely expressed in excitatory neurons but not in inhibitory neurons. In the developing olfactory bulb, Homer 1b/c and Cupidin/Homer 2a/b are up-regulated in the granular, external plexiform, and glomerular layers, whereas Homer 3a/b drastically decreases in these regions within the first postnatal week. Cupidin/Homer 2a/b is also expressed in olfactory sensory neurons within a distinct olfactory epithelial zone and is then widely distributed to both the axons in the olfactory nerve layer and the cilia in the olfactory epithelium. These results demonstrate that Homer family members have distinct regional, cellular, and subcellular distributions in time and space during postnatal brain development.

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NMDA Receptor Stimulation and Brain-Derived Neurotrophic Factor Upregulate Homer 1a mRNA via the Mitogen-Activated Protein Kinase Cascade in Cultured Cerebellar Granule Cells

Cited by 125 publications

References 36 publications

Synaptic Activity-Induced Conversion of Intronic to Exonic Sequence in Homer 1 Immediate Early Gene Expression

Synaptic Activity-Induced Conversion of Intronic to Exonic Sequence in Homer 1 Immediate Early Gene Expression

Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia

Differential expression of Homer family proteins in the developing mouse brain

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