Identification of CAMTA1 target genes in the adult mouse hippocampus
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE62122 | GEO | 2016/05/20
SECONDARY ACCESSION(S): PRJNA263249
REPOSITORIES: GEO
Similar Datasets
Project description:Calmodulin sits at the center of molecular mechanisms underlying learning and memory. Its complex, and sometimes opposite, influences via the binding to various proteins are yet to be fully understood. Calcium/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) both bind open calmodulin, favoring Long-term-potentiation (LTP) or depression (LTD) respectively. Neurogranin binds to the closed conformation of calmodulin and its impact on synaptic plasticity is less clear. We set up a mechanistic computational model based on allosteric principles to simulate calmodulin state transitions and its interaction with calcium ions and the three binding partners mentioned above. We simulated calcium spikes at various frequencies and show that neurogranin regulates synaptic plasticity along three modalities. At low spike frequencies, neurogranin inhibits the onset of LTD by limiting CaN activation. At intermediate frequencies, neurogranin limits LTP by precluding binding of CaMKII with calmodulin. Finally, at high spike frequencies, neurogranin promotes LTP by enhancing CaMKII autophosphorylation. While neurogranin might act as a calmodulin buffer, it does not significantly preclude the calmodulin opening by calcium. On the contrary, neurogranin synchronizes the opening of calmodulin's two lobes and promotes their activation at specific frequencies, increasing the chance of CaMKII trans-autophosphorylation. Importantly, the positive effect of neurogranin on CaMKII activation is mediated via CaN, and too few or too much CaN will abolish this effect. Furthermore, the amount of neurogranin itself differentially regulates the levels of CaN and CaMKII activities, as well as the frequencies at which the balance switch from one to the other.
2019-12-18 | MODEL1903010001 | BioModels
Project description:Calcium has been shown to be an important signalling molecule in the transduction of abiotic stress signals in Arabidopsis thaliana. Alteration of the calcium signature through the use of inhibitors has been shown to result in changes in the expression of certain downstream abiotic stress-induced genes. However, the communication of this signal through specific calcium-sensitive intermediate molecules has remained poorly elucidated. Various candidate molecules exist and including calcinurin, calcium-dependent protein kinases and calmodulin. Recently, a screen of an Arabidopsis thaliana cDNA expression library with calmodulin resulted in the isolation of the protein designated calmodulin-binding transcriptional activator or AtCAMTA that may function as one of these calcium-sensitive intermediate molecules. The Arabidopsis genome contains six CAMTA genes (AtCAMTA1-6), all of which are expressed in varying tissues throughout development. AtCAMTA1 was shown to function as a transcriptional activator through the expression of a chimeric protein consisting of the bacteria LexA protein fused to various segments of AtCAMTA expressed in yeast. In order to identify putative target genes of AtCAMTA1 in Arabidopsis we plan to analyse the transcriptome of AtCAMTA1 loss-of-function mutants. The gene expression pattern of two previously characterised alleles of AtCAMTA1 will be compared to wild type. Experimenter name = Sarah Scrase-Field; Experimenter phone = 01865 275062; Experimenter fax = 01865 275074; Experimenter department = University of Oxford; Experimenter address = Department of Plants Sciences; Experimenter address = University of Oxford; Experimenter address = South Parks Road; Experimenter address = Oxford; Experimenter zip/postal_code = OX1 3RB; Experimenter country = UK Experiment Overall Design: 4 samples were used in this experiment
2008-06-13 | E-GEOD-5618 | biostudies-arrayexpress
Project description:Li2012 Calcium mediated synaptic
plasticity
This model is an extension of
BIOMD0000000183.
This model is described in the article:
Calcium input frequency,
duration and amplitude differentially modulate the relative
activation of calcineurin and CaMKII.
Li L, Stefan MI, Le Novère
N.
PLoS ONE 2012; 7(9): e43810
Abstract:
NMDA receptor dependent long-term potentiation (LTP) and
long-term depression (LTD) are two prominent forms of synaptic
plasticity, both of which are triggered by post-synaptic
calcium elevation. To understand how calcium selectively
stimulates two opposing processes, we developed a detailed
computational model and performed simulations with different
calcium input frequencies, amplitudes, and durations. We show
that with a total amount of calcium ions kept constant, high
frequencies of calcium pulses stimulate calmodulin more
efficiently. Calcium input activates both calcineurin and
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) at all
frequencies, but increased frequencies shift the relative
activation from calcineurin to CaMKII. Irrespective of
amplitude and duration of the inputs, the total amount of
calcium ions injected adjusts the sensitivity of the system to
calcium input frequencies. At a given frequency, the quantity
of CaMKII activated is proportional to the total amount of
calcium. Thus, an input of a small amount of calcium at high
frequencies can induce the same activation of CaMKII as a
larger amount, at lower frequencies. Finally, the extent of
activation of CaMKII signals with high calcium frequency is
further controlled by other factors, including the availability
of calmodulin, and by the potency of phosphatase
inhibitors.
This model is hosted on
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and identified by:
BIOMD0000000628.
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To the extent possible under law, all copyright and related or
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2015-12-10 | BIOMD0000000628 | BioModels
Project description:Screening of cDNA expression libraries with labelled calmodulin (CaM) as a probe resulted in the isolation of cDNA encoding proteins designated CAMTA (for calmodulin-binding transcription activators). The Arabidopsis genome contains 6 members of this protein family (AtCAMTA1-6) all containing in addition to a defined CaM-binding domain a DNA-binding domain and ankyrin-repeat motifs. RT-PCR analysis revealed that all 6 genes are expressed in all organ throughout plant development. Therefore functional regulation of AtCAMTA proteins is likely mediated by second messengers (e.g. calcium/calmodulin signalling) and protein levels rather than by or in addition to gene expression levels. Based on domain organisation and sequence homologies we identified putative members of this protein family in C. elegans and in human. A yeast system was used to express chimeric fusion proteins comprised of the DNA-binding domain of the bacterial LexA protein with various segments of AtCAMTA1. This analysis revealed a distinct domain of AtCAMTA1 capable of activating transcription. Similar results were obtained with two human CAMTA homologues. To identify the gene targets of CAMTA proteins in Arabidopsiswe plan to analyse the transcriptome in loss_of_function and gain_of_function AtCAMTA mutants. For this we have already isolated a T-DNA insertion mutant of AtCAMTA1 (two alleles) and have requested two other insertion mutants of AtCAMTA2 and AtCAMTA3 identified in other labs. Screening for insertion mutants in the three remaining genes is underway. In addition we have initiated a gain_of_function approach in which DL10 proteins are expressed under the control of the dexamethasone-inducible promoter. Genes whose expression will be found modulated in the mutant plants will be considered candidate targets of AtCAMTA proteins. This analysis will complement an in vitro study of DNA-protein interactions to identify target-binding sites (part of the BBSRC funded project). As a first step in the project proposed to GARNet we suggest to compare the transcriptome in WT whole plants (2 weeks old) with that of three T-DNA insertion AtCAMTA mutants and one line expressing AtCAMTA1 under the control of an inducible promoter.
2022-11-21 | E-NASC-26 | biostudies-arrayexpress
Project description:Arabidopsis thaliana Col-0 as a wild type and camta1/2/3/sid2-1 as a mutant were compared in their gene expression at the end of day. By comparing the transcriptomes, we showed the presence of SA-independent and CAMTA-dependent pathway at ambient temperature.
2016-12-31 | GSE87506 | GEO
Project description:Screening of cDNA expression libraries with labelled calmodulin (CaM) as a probe resulted in the isolation of cDNA encoding proteins designated CAMTA (for calmodulin-binding transcription activators). The Arabidopsis genome contains 6 members of this protein family (AtCAMTA1-6) all containing in addition to a defined CaM-binding domain a DNA-binding domain and ankyrin-repeat motifs. RT-PCR analysis revealed that all 6 genes are expressed in all organ throughout plant development. Therefore functional regulation of AtCAMTA proteins is likely mediated by second messengers (e.g. calcium/calmodulin signalling) and protein levels rather than by or in addition to gene expression levels. Based on domain organisation and sequence homologies we identified putative members of this protein family in C. elegans and in human. A yeast system was used to express chimeric fusion proteins comprised of the DNA-binding domain of the bacterial LexA protein with various segments of AtCAMTA1. This analysis revealed a distinct domain of AtCAMTA1 capable of activating transcription. Similar results were obtained with two human CAMTA homologues. To identify the gene targets of CAMTA proteins in Arabidopsiswe plan to analyse the transcriptome in loss_of_function and gain_of_function AtCAMTA mutants. For this we have already isolated a T-DNA insertion mutant of AtCAMTA1 (two alleles) and have requested two other insertion mutants of AtCAMTA2 and AtCAMTA3 identified in other labs. Screening for insertion mutants in the three remaining genes is underway. In addition we have initiated a gain_of_function approach in which DL10 proteins are expressed under the control of the dexamethasone-inducible promoter. Genes whose expression will be found modulated in the mutant plants will be considered candidate targets of AtCAMTA proteins. This analysis will complement an in vitro study of DNA-protein interactions to identify target-binding sites (part of the BBSRC funded project). As a first step in the project proposed to GARNet we suggest to compare the transcriptome in WT whole plants (2 weeks old) with that of three T-DNA insertion AtCAMTA mutants and one line expressing AtCAMTA1 under the control of an inducible promoter. Experiment Overall Design: 5 samples
2008-06-14 | E-GEOD-6156 | biostudies-arrayexpress
Project description:Calcium has been shown to be an important signalling molecule in the transduction of abiotic stress signals in Arabidopsis thaliana. Alteration of the calcium signature through the use of inhibitors has been shown to result in changes in the expression of certain downstream abiotic stress-induced genes. However, the communication of this signal through specific calcium-sensitive intermediate molecules has remained poorly elucidated. Various candidate molecules exist and including calcinurin, calcium-dependent protein kinases and calmodulin. Recently, a screen of an Arabidopsis thaliana cDNA expression library with calmodulin resulted in the isolation of the protein designated calmodulin-binding transcriptional activator or AtCAMTA that may function as one of these calcium-sensitive intermediate molecules. The Arabidopsis genome contains six CAMTA genes (AtCAMTA1-6), all of which are expressed in varying tissues throughout development. AtCAMTA1 was shown to function as a transcriptional activator through the expression of a chimeric protein consisting of the bacteria LexA protein fused to various segments of AtCAMTA expressed in yeast. In order to identify putative target genes of AtCAMTA1 in Arabidopsis we plan to analyse the transcriptome of AtCAMTA1 loss-of-function mutants. The gene expression pattern of two previously characterised alleles of AtCAMTA1 will be compared to wild type. Experimenter name = Sarah Scrase-Field Experimenter phone = 01865 275062 Experimenter fax = 01865 275074 Experimenter department = University of Oxford Experimenter address = Department of Plants Sciences Experimenter address = University of Oxford Experimenter address = South Parks Road Experimenter address = Oxford Experimenter zip/postal_code = OX1 3RB Experimenter country = UK Keywords: genetic_modification_design
2007-01-08 | GSE5618 | GEO
Project description:Social communication guides decision making that is essential for survival. Social transmission of food preference (STFP) is an ecologically relevant memory paradigm in which an animal learns a desirable food odor from other animals in a social context. How food-preference memory is acquired, consolidated, and stored is unclear. Here, we identify a circuit involving the posteromedial nucleus of the cortical amygdala (COApm) as a computational center that integrates social and sensory olfactory inputs for long-term STFP memory consolidation. Blocking synaptic signaling by the COApm circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage, or recall. STFP memory consolidation by the COApm depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus and requires protein synthesis, suggesting a gene expression mechanism. Deep single-cell and spatial transcriptomics revealed robust but distinct gene expression signatures induced by STFP memory formation in the COApm consistent with synapse restructuring. Our data thus define a neural circuit for consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein synthesis-dependent memory consolidation from memory acquisition, storage, or retrieval.
2024-03-09 | GSE256522 | GEO
Project description:Aging is a complex biological process that compromises brain function and neuronal network activity, leading to cognitive decline and synaptic dysregulation. In recent years, a cyclic Ketogenic Diet (KD) has emerged as a potential treatment to ameliorate cognitive decline by improving memory in aged mice after long-term administration. However, whether short-term cyclic KD administration later in life preserves memory has not been addressed in detail. Accordingly, here we investigated how a short-term cyclic KD starting at 20-23 months-old regulates brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings revealed that a cyclic KD improves working memory and hippocampal LTP in 24-27 months-old mice after 16 weeks of treatment. Moreover, the diet also promotes higher dendritic arborization complexity and dendritic spine density in the prefrontal cortex. Furthermore, to elucidate the molecular mechanisms underlying the memory improvements elicited by a cyclic KD, cortical synaptosomes of aged mice fed with this diet for 1 year were analyzed by mass spectrometry. Bioinformatics analysis revealed that long-term cyclic KD administration predominantly modulates the presynaptic compartment by inducing changes in the cAMP/PKA signaling pathway, the synaptic vesicle cycle and the actin/microtubule cytoskeleton. To test these findings in vivo, synaptic proteins from cortices of 24-27 month-old mice fed with control or cyclic KD for 16 weeks were analyzed by western blot. Interestingly, increased Brain Derived Neurotrophic Factor abundance, MAP2 phosphorylation and PKA activity were observed. Overall, we show that a cyclic KD regulates brain function and memory even when it is administered at late mid-life and significantly triggers several molecular features of long-term administration, including the PKA signaling pathway and cytoskeleton dynamics, thus promoting synaptic plasticity at advanced age.
2023-08-08 | MSV000092626 | MassIVE
Project description:Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, precise regulation of calmodulin expression may be an important for regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated post-transcriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3’-untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through the calcineurin to NFAT. miR-1 also negatively regulated expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium-signaling components calmodulin, Mef2a, and Gata4.
2009-03-05 | GSE13874 | GEO