Abstract:
:Oligophrenin-1 (OPHN1) encodes a Rho-GTPase-activating protein (Rho-GAP) whose loss of function has been associated with X-linked mental retardation (MR). The pathophysiological role of OPHN1, however, remains poorly understood. Here we show that OPHN1 through its Rho-GAP activity plays a critical role in the activity-dependent maturation and plasticity of excitatory synapses by controlling their structural and functional stability. Synaptic activity through NMDA receptor activation drives OPHN1 into dendritic spines, where it forms a complex with AMPA receptors, and selectively enhances AMPA-receptor-mediated synaptic transmission and spine size by stabilizing synaptic AMPA receptors. Consequently, decreased or defective OPHN1 signaling prevents glutamatergic synapse maturation and causes loss of synaptic structure, function, and plasticity. These results imply that normal activity-driven glutamatergic synapse development is impaired by perturbation of OPHN1 function. Thus, our findings link genetic deficits in OPHN1 to glutamatergic dysfunction and suggest that defects in early circuitry development are an important contributory factor to this form of MR.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Nadif Kasri N,Nakano-Kobayashi A,Malinow R,Li B,Van Aelst Ldoi
10.1101/gad.1783809subject
Has Abstractpub_date
2009-06-01 00:00:00pages
1289-302issue
11eissn
0890-9369issn
1549-5477pii
23/11/1289journal_volume
23pub_type
杂志文章abstract::Specific recognition of splice sites within metazoan mRNA precursors (pre-mRNAs) is a potential stage for gene regulation by alternative splicing. Splicing factors of the SR protein family play a major role in this regulation, as they are required for early recognition of splice sites during spliceosome assembly. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.740
更新日期:1999-03-15 00:00:00
abstract::Human ELAV proteins are implicated in cell growth and differentiation via regulation of mRNA expression in the cytoplasm. In human embryonic teratocarcinoma (hNT2) cells transfected with the human neuronal ELAV-like protein, Hel-N1, neurites formed, yet cells were not terminally differentiated. Cells in which neurite ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.4.449
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abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
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doi:10.1101/gad.417707
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abstract::The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein ...
journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1534807
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abstract::H4K20 methylation is a broad chromatin modification that has been linked with diverse epigenetic functions. Several enzymes target H4K20 methylation, consistent with distinct mono-, di-, and trimethylation states controlling different biological outputs. To analyze the roles of H4K20 methylation states, we generated c...
journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2006-11-01 00:00:00
abstract::Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive muta...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.270421.115
更新日期:2015-10-15 00:00:00
abstract::Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...
journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.21.2828
更新日期:1999-11-01 00:00:00
abstract::Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1120
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abstract::Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1793409
更新日期:2009-06-15 00:00:00
abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1823109
更新日期:2009-08-15 00:00:00
abstract::Nitric oxide (NO) is an important second messenger involved in numerous biological processes, but how it regulates gene expression is not well understood. In this issue of Genes & Development, Cáceres and colleagues (pp. 1476-1485) report a critical requirement of NO as a direct regulator of gene expression through it...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2080411
更新日期:2011-07-15 00:00:00
abstract::The bHLH-PAS transcription factor SIM1 is expressed during the development of the hypothalamic-pituitary axis in three hypothalamic nuclei: the paraventricular nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic nucleus (SON). To investigate Sim1 function in the hypothalamus, we produced mice...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.20.3264
更新日期:1998-10-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1643308
更新日期:2008-05-01 00:00:00
abstract::The Hox-2 locus on chromosome 11 represents one of the major clusters of homeo-box-containing genes in the mouse. We have identified two new members (Hox-2.6 and Hox-2.7), which form part of this cluster of seven linked genes, and it appears that the Hox-2 locus is related by duplication and divergence to at least one...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.11.1424
更新日期:1988-11-01 00:00:00
abstract::The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 ar...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.305037.117
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abstract::Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to...
journal_title:Genes & development
pub_type: 杂志文章
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abstract::In murine plasmacytoma and human Burkitt's lymphoma cells, one allele of c-myc is translocated into one of the immunoglobulin loci, resulting in a characteristic pattern of deregulated c-myc transcription. Translocation events between c-myc and the IgH locus segregate c-myc and the IgH intron enhancer to different rec...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.18.2212
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journal_title:Genes & development
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abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
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更新日期:2016-07-01 00:00:00
abstract::The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of the pregastrulation embryo and stem cell lines derived from the early embryo. Osteopontin (OPN) is a protein secreted by cells of the preimplantation embryo and contains a GRGDS motif that can bind to specific integrin ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.13.2073
更新日期:1998-07-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1627008
更新日期:2008-02-15 00:00:00
abstract::Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potent...
journal_title:Genes & development
pub_type: 杂志文章,评审
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更新日期:2013-11-15 00:00:00
abstract::This paper examines ovarian transcription of the divergently oriented yolk protein genes 1 and 2 (yp1 and yp2) of Drosophila melanogaster. We report germ line transformation results demonstrating that yp1 and yp2 are transcribed in the same subpopulations of ovarian follicle cells. Our results show that this expressio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.613
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.230302
更新日期:2002-05-01 00:00:00
abstract::The Neurospora crassa clock-controlled gene (ccg-2) is transcriptionally activated by the circadian clock in a time-of-day-specific manner. Transcript and sequence analyses of ccg-2 reveal that the predicted Ccg-2 polypeptide bears significant similarity to a class of low-molecular-weight, cysteine-rich, hydrophobic p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2382
更新日期:1992-12-01 00:00:00