Developmental regulation of Ubc9 in the rat nervous system.

2008 ◽  
Vol 55 (4) ◽  
pp. 681-686 ◽  
Author(s):  
Mutsufusa Watanabe ◽  
Kaoru Takahashi ◽  
Kayoko Tomizawa ◽  
Hidehiro Mizusawa ◽  
Hiroshi Takahashi
Keyword(s):  
Protein Modification ◽  
Pyramidal Neurons ◽  
Hippocampal Formation ◽  
Developmental Regulation ◽  
Covalent Modification ◽  
Adult Brain ◽  
Modification System ◽  
Neuronal Stem Cells ◽  
Protein Levels ◽  
Conjugating Enzyme

The SUMO-conjugating enzyme Ubc9 is an essential enzyme in the SUMO (small ubiquitin-related modifier) protein modification system. Although sumoylation, covalent modification of cellular proteins by SUMO, is considered to regulate various cellular processes, and many substrates for sumoylation have been identified recently, the regulation of Ubc9 expression has not been examined in detail. We analyzed the expression of Ubc9 during rat brain development at the mRNA and protein levels. Northern and Western blot analyses revealed that expression of Ubc9 and SUMO-1 was developmentally regulated, while that of the ubiquitin-conjugating enzyme UbcH7 did not change so dramatically. In situ hybridization analysis revealed that the expression of Ubc9 was high in neuronal stem cells and moderate in differentiated neurons at embryonic stages. In the adult brain, moderate expression was observed in subsets of neurons, such as the dentate granular neurons and pyramidal neurons in the hippocampal formation and the large pyramidal neurons in the cerebral cortex. These results suggest that the Ubc9-SUMO system might participate in the proliferation and differentiation of neuronal cells in the developing brain and in neuronal plasticity in the adult brain.

Structural plasticity and tianeptine: cellular and molecular targets

2002 ◽  
Vol 17 (S3) ◽  
pp. 318s-330s ◽  
Author(s):  
B.S. McEwen ◽  
A.M. Magarinos ◽  
L.P. Reagan
Keyword(s):  
Animal Model ◽  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Formation ◽  
Stress Hormones ◽  
Structural Plasticity ◽  
Depressive Illness ◽  
Adult Brain ◽  
Gamma Aminobutyric Acid ◽  
Age Related

SummaryThe hippocampal formation, a structure involved in declarative, spatial and contextual memory, undergoes atrophy in depressive illness along with impairment in cognitive function. Animal model studies have shown that the hippocampus is a particularly sensitive and vulnerable brain region that responds to stress and stress hormones. Studies on models of stress and glucocorticoid actions reveal that the hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes remodeling of dendrites in the CA3 region, a region that is particularly important in memory processing. Both forms of structural remodeling of the hippocampus are mediated by adrenal steroids working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, head trauma, and ischemia, and alterations of calcium homeostasis that accompany age-related cognitive impairment. Tianeptine (tianeptine) is an effective antidepressant that prevents and even reverses the actions of stress and glucocorticoids on dendritic remodeling in an animal model of chronic stress. Multiple neurotransmitter systems contribute to dendritic remodeling, including EAA, serotonin, and gamma-aminobutyric acid (GABA), working synergistically with glucocorticoids. This review summarizes findings on neurochemical targets of adrenal steroid actions that may explain their role in the remodeling process. In studying these actions, we hope to better understand the molecular and cellular targets of action of tianeptine in relation to its role in influencing structural plasticity of the hippocampus.

scholarly journals PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor α Signaling in Human Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 623
Author(s):  
Marit Rasmussen ◽  
Susanna Tan ◽  
Venkata S. Somisetty ◽  
David Hutin ◽  
Ninni Elise Olafsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Protein Modification ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Transactivation Domain ◽  
Adp Ribosylation ◽  
Protein Levels ◽  
17Β Estradiol ◽  
Mcf 7

ADP-ribosylation is a post-translational protein modification catalyzed by a family of proteins known as poly-ADP-ribose polymerases. PARP7 (TIPARP; ARTD14) is a mono-ADP-ribosyltransferase involved in several cellular processes, including responses to hypoxia, innate immunity and regulation of nuclear receptors. Since previous studies suggested that PARP7 was regulated by 17β-estradiol, we investigated whether PARP7 regulates estrogen receptor α signaling. We confirmed the 17β-estradiol-dependent increases of PARP7 mRNA and protein levels in MCF-7 cells, and observed recruitment of estrogen receptor α to the promoter of PARP7. Overexpression of PARP7 decreased ligand-dependent estrogen receptor α signaling, while treatment of PARP7 knockout MCF-7 cells with 17β-estradiol resulted in increased expression of and recruitment to estrogen receptor α target genes, in addition to increased proliferation. Co-immunoprecipitation assays revealed that PARP7 mono-ADP-ribosylated estrogen receptor α, and mass spectrometry mapped the modified peptides to the receptor’s ligand-independent transactivation domain. Co-immunoprecipitation with truncated estrogen receptor α variants identified that the hinge region of the receptor is required for PARP7-dependent mono-ADP-ribosylation. These results imply that PARP7-mediated mono-ADP-ribosylation may play an important role in estrogen receptor positive breast cancer.

scholarly journals Maternal immune activation induces methylation changes in schizophrenia genes

2022 ◽  
Author(s):  
Tom Johnson ◽  
Defne Saatci ◽  
Lahiru Handunnetthi
Keyword(s):  
Environmental Risk ◽  
Immune Activation ◽  
Pyramidal Neurons ◽  
Fold Change ◽  
Adult Brain ◽  
Maternal Immune Activation ◽  
Differentially Methylated Genes ◽  
A Cell ◽  
Layer V ◽  
Upregulated Genes

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57 , FDR = 0.049) and gestational day 17 (fold change = 1.97 , FDR = 0.0006). We also found that downregulated genes in GABAergic Rosehip interneurons were enriched among hypermethylated genes at gestational day 17 (fold change = 1.62, FDR= 0.03). Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.

Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain

2005 ◽  
Vol 490 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Jesús Mariano Ureña ◽  
Anna La Torre ◽  
Albert Martínez ◽  
Eve Lowenstein ◽  
Neus Franco ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Developmental Regulation ◽  
Adult Brain ◽  
Synaptic Localization

scholarly journals Developmental Regulation of Basket Interneuron Synapses and Behavior through NCAM in Mouse Prefrontal Cortex

2020 ◽  
Vol 30 (8) ◽  
pp. 4689-4707
Author(s):  
Chelsea S Sullivan ◽  
Vishwa Mohan ◽  
Paul B Manis ◽  
Sheryl S Moy ◽  
Young Truong ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Developmental Regulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Electrophysiological Recording ◽  
Network Function ◽  
Growth Cone Collapse ◽  
Layer 2 ◽  
And Behavior

Abstract Parvalbumin (PV)-expressing basket interneurons in the prefrontal cortex (PFC) regulate pyramidal cell firing, synchrony, and network oscillations. Yet, it is unclear how their perisomatic inputs to pyramidal neurons are integrated into neural circuitry and adjusted postnatally. Neural cell adhesion molecule NCAM is expressed in a variety of cells in the PFC and cooperates with EphrinA/EphAs to regulate inhibitory synapse density. Here, analysis of a novel parvalbumin (PV)-Cre: NCAM F/F mouse mutant revealed that NCAM functions presynaptically in PV+ basket interneurons to regulate postnatal elimination of perisomatic synapses. Mutant mice exhibited an increased density of PV+ perisomatic puncta in PFC layer 2/3, while live imaging in mutant brain slices revealed fewer puncta that were dynamically eliminated. Furthermore, EphrinA5-induced growth cone collapse in PV+ interneurons in culture depended on NCAM expression. Electrophysiological recording from layer 2/3 pyramidal cells in mutant PFC slices showed a slower rise time of inhibitory synaptic currents. PV-Cre: NCAM F/F mice exhibited impairments in working memory and social behavior that may be impacted by altered PFC circuitry. These findings suggest that the density of perisomatic synapses of PV+ basket interneurons is regulated postnatally by NCAM, likely through EphrinA-dependent elimination, which is important for appropriate PFC network function and behavior.

scholarly journals Dendritic right/left asymmetries in the neurons of the human hippocampal formation: a quantitative Golgi study

2007 ◽  
Vol 65 (4b) ◽  
pp. 1105-1113 ◽  
Author(s):  
Maria José Sá ◽  
Carlos Ruela ◽  
Maria Dulce Madeira
Keyword(s):  
Pyramidal Neurons ◽  
Right Hemisphere ◽  
Granule Cells ◽  
Hippocampal Formation ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Volumetric Analysis ◽  
Golgi Study ◽  
Dendritic Trees ◽  
The Right

OBJECTIVE: To search for right/left asymmetries in the dendritic trees of the neuronal populations and in the cell-free layer volumes of the human hipoccampal formation. METHOD: In necropsic material obtained from six male individuals we performed a quantitative Golgi study of the dendritic trees of dentate granules, CA3 and CA1 pyramidal neurons and a volumetric analysis of dentate gyrus molecular layer, strata oriens plus alveus and strata lacunosum-moleculare plus radiatum of CA3 and CA1 fields. RESULTS: We found inter-hemispheric asymmetries in the dendrites trees of all neurons, reaching the significant level in the number of granule cells dendritic segments (higher in the left than in the right hemisphere), dendritic branching density of CA3 pyramidal cells and mean dendritic length of CA1 apical terminal segments (higher in the right than in the opposite side). No volumetric differences were observed. CONCLUSION: This study points to different anatomical patterns of connectivity in the hippocampal formations of both hemispheres which may underlie functional asymmetries.

NADPH-diaphorase reactive pyramidal neurons in Ammon's horn and the subiculum of the rat hippocampal formation

1996 ◽  
Vol 733 (1) ◽  
pp. 31-40 ◽  
Author(s):  
R. Roy Vaid ◽  
Benjamin K. Yee ◽  
J.N.P. Rawlins ◽  
Susan Totterdell
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Formation ◽  
Nadph Diaphorase ◽  
Ammon's Horn ◽  
Ammon’S Horn

scholarly journals The Small Ubiquitin-like Modifier (SUMO) Protein Modification System inArabidopsis

2002 ◽  
Vol 278 (9) ◽  
pp. 6862-6872 ◽  
Author(s):  
Jasmina Kurepa ◽  
Joseph M. Walker ◽  
Jan Smalle ◽  
Mark M. Gosink ◽  
Seth J. Davis ◽  
...  
Keyword(s):  
Protein Modification ◽  
Modification System ◽  
Sumo Protein

scholarly journals Elevating the level of Cdc34/Ubc3 ubiquitin-conjugating enzyme in mitosis inhibits association of CENP-E with kinetochores and blocks the metaphase alignment of chromosomes

2001 ◽  
Vol 154 (4) ◽  
pp. 707-718 ◽  
Author(s):  
Leana M. Topper ◽  
Holger Bastians ◽  
Joan V. Ruderman ◽  
Gary J. Gorbsky
Keyword(s):  
Mammalian Cells ◽  
Proteasome Inhibitors ◽  
Metaphase Plate ◽  
Cytoplasmic Dynein ◽  
Mitogen Activated Protein Kinase ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Associated Proteins ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

Cdc34/Ubc3 is a ubiquitin-conjugating enzyme that functions in targeting proteins for proteasome-mediated degradation at the G1 to S cell cycle transition. Elevation of Cdc34 protein levels by microinjection of bacterially expressed Cdc34 into mammalian cells at prophase inhibited chromosome congression to the metaphase plate with many chromosomes remaining near the spindle poles. Chromosome condensation and nuclear envelope breakdown occurred normally, and chromosomes showed oscillatory movements along mitotic spindle microtubules. Most injected cells arrested in a prometaphase-like state. Kinetochores, even those of chromosomes that failed to congress, possessed the normal trilaminar plate ultrastructure. The elevation of Cdc34 protein levels in early mitosis selectively blocked centromere protein E (CENP-E), a mitotic kinesin, from associating with kinetochores. Other proteins, including two CENP-E–associated proteins, BubR1 and phospho-p42/p44 mitogen-activated protein kinase, and mitotic centromere-associated kinesin, cytoplasmic dynein, Cdc20, and Mad2, all exhibited normal localization to kinetochores. Proteasome inhibitors did not affect the prometaphase arrest induced by Cdc34 injection. These studies suggest that CENP-E targeting to kinetochores is regulated by ubiquitylation not involving proteasome-mediated degradation.

Silent Synapses in the Immature Visual Cortex: Layer-Specific Developmental Regulation

2004 ◽  
Vol 91 (2) ◽  
pp. 1097-1101 ◽  
Author(s):  
Simon Rumpel ◽  
Gunnar Kattenstroth ◽  
Kurt Gottmann
Keyword(s):  
Visual Cortex ◽  
Pyramidal Neurons ◽  
Developmental Regulation ◽  
Pyramidal Cells ◽  
Cortical Plate ◽  
Glutamatergic Synapses ◽  
Silent Synapses ◽  
Deep Layers ◽  
Further Development ◽  
Layer Vi

Central glutamatergic synapses are thought to initially form as immature, so-called silent synapses showing exclusively N-methyl-d-aspartate receptor-mediated synaptic transmission. Postsynaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors during further development leads to a conversion into functional, mature synapses. Here, we tested the hypothesis that, according to the “inside first–outside last” pattern of neocortical layer formation and synaptogenesis, pyramidal cells in the superficial layers might show a higher fraction of silent synapses compared with pyramidal cells in the deep layers. We performed an electrophysiological analysis of glutamatergic synapses in acute rat visual cortex slices during postnatal development. In layer VI pyramidal neurons the incidence of silent synapses was high during the first postnatal week and strongly declined during further development. Surprisingly, in superficial cortical plate pyramidal neurons (immature layers II/III), the fraction of silent synapses was initially very low and increased up to the second postnatal week. Thereafter, a similar decline as found in layer VI pyramidal neurons was observed. Thus the developmental regulation of silent synapses was clearly different in pyramidal neurons from different neocortical layers. The almost complete absence of silent synapses at early stages in layer II/III pyramidal neurons indicates that an initially formed subset of synapses is constitutively functional. This might be important to enable spontaneous activity and latter activity-dependent maturation of synapses.

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