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The Global ETD Search service is a free service for researchers
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Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 11 to 19 of 19 (0.107 seconds)| 11 |
Protein phosphorylation : roles in subcellular localization and synaptic plasticity /Davies, Kurtis Daniel January 2008 (has links)
Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 100-118).
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Regulation of tubulin heterodimer partitioning during interphase and mitosis /Holmfeldt, Per, January 2008 (has links)
Diss. (sammanfattning) Umeå : Umeå universitet, 2008. / Härtill 4 uppsatser.
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Calmodulin mediated regulation of NF-kappaB in lymphocytes /Edin, Sofia, January 2008 (has links)
Diss. (sammanfattning) Umeå : Univ., 2008. / Härtill 4 uppsatser.
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Memória metabólica de células beta pancreática controla a secreção de insulina e é mediada pela CaMKII = Metabolic memory of pancreatic beta cell controls insulin secretion and is mediated by CaMKII / Metabolic memory of pancreatic beta cell controls insulin secretion and is mediated by CaMKIISantos, Gustavo Jorge, 1986- 24 August 2018 (has links)
Orientadores: Antonio Carlos Boschiero, Luiz Fernando de Rezende / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-24T14:18:46Z (GMT). No. of bitstreams: 1
Santos_GustavoJorge_D.pdf: 3129731 bytes, checksum: b00bd77f6b06be14f135a76b6977ca47 (MD5)
Previous issue date: 2014 / Resumo: Introdução: A Cálcio-Calmodulina quinase II (CaMKII) atua tanto na regulação da secreção de insulina com de neurotransmissores pela mesma via de sinalização. Além disso, a CaMKII é conhecida por ser a "molécula da memória", pois sua atividade é fundamental em sua formação. Portanto, hipotetizamos que células ß pancreática tem a capacidade de adquirir e estocar informações contidas em pulsos de cálcio, formando uma memória metabólica. Métodos: Para comprovar nossa hipótese, desenvolvemos um novo paradigma de exposição de células ? a pulsos de 30 mM de glicose, seguido de uma período de consolidação (24 hrs) para excluir qualquer efeito agudo do metabolismo da glicose. Após esse período analizamos a secreção de insulina (RIA), expressão proteica (Western blot), a resposta secretória frente a uma "rampa de glicose" e o Ca2+ citoplasmático induzido por glicose. Resultados: Células ß expostas a pulsos de glicose (30 mM) mostraram maior secreção de insulina estimulada por glucose, evidenciando a memória metabólica a qual foi totalmente dependente a CaMKII. Esse fenômeno foi refletido na expressão proteica de proteínas importantes na sinalização do cálcio e na secreção de insulina. Além disso, células expostas ao regime de pulsos de glucose apresentaram maior expressão do MAFA, um fator de transcrição chave para a função da célula ß. Conclusão: Em suma, assim como neurônios, células ß tumorais (MIN6), ilhotas de camundongos e de humanos são capazes de adquirir, estocar e evocar informações / Abstract: Backgroun: Ca2+/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Memory is the ability to acquire, to store and to evocate any kind of information. In CNS, the process behind this phenomenon in the Long-Term Potentiation (LTP) and is known that it requires Ca2+ to occur. In additional, CaMKII is necessary to store information during LTP. In pancreatic ß-cells, CaMKII plays pivotal role during GSIS process. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in Ca2+ pulses as a form of "metabolic memory", just as neurons store cognitive information. Methods: To test this hypothesis, we developed a novel paradigm of pulsed exposure of mice and human ß-cells to intervals of high glucose, followed by a 24-hour consolidation period to eliminate any acute metabolic effects. After this period, we analyzed insulin secretion (by RIA), protein expression (by Western blot), response to a glucose-ramp and the glucose-induced Ca2+ influx. Results: Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was entirely dependent on CaMKII. We also observed, in pulse group, an increase in Ca2+ influx induced by glucose. In additional, metabolic memory was reflected on the protein level by increased expression of proteins involved in GSIS and Ca2+-dependent vesicle secretion, such as GCK, Cav1.2, SNAP25, pCaMKII and pSynapsin. Finally, we observed in human islet elevated levels of the key ß cell transcription factor MAFA. Discussion: Based on or findings we conclude that pancreatic ß cells, either from mice or humans, have the ability to acquire, store and retrieve information. This process is CaMKII-dependent and is due to modifications in the glucose-sensing machinery of the cell, since we observed an increase in GSIS and Ca2+ influx together with an increase in several proteins involved in this process. Our findings suggests that MAFA is the key effector in this memory, since (a) it is a potent activator of insulin gene, (b)is activated by CaMKII and (c) its expression is increased even 24 hours after the last pulse. Conclusion: In summary, like neurons, human and mouse ß-cells are able to acquire and retrieve information / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular
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Induction and Maintenance of Synaptic PlasticityGraupner, Michael 11 September 2008 (has links) (PDF)
Synaptic long-term modifications following neuronal activation are believed to be at the origin of learning and long-term memory. Recent experiments suggest that these long-term synaptic changes are all-or-none switch-like events between discrete states of a single synapse. The biochemical network involving calcium/calmodulin-dependent protein kinase II (CaMKII) and its regulating protein signaling cascade has been hypothesized to durably maintain the synaptic state in form of a bistable switch. Furthermore, it has been shown experimentally that CaMKII and associated proteins such as protein kinase A and calcineurin are necessary for the induction of long-lasting increases (long-term potentiation, LTP) and/or long-lasting decreases (long-term depression, LTD) of synaptic efficacy. However, the biochemical mechanisms by which experimental LTP/LTD protocols lead to corresponding transitions between the two states in realistic models of such networks are still unknown. We present a detailed biochemical model of the calcium/calmodulin-dependent autophosphorylation of CaMKII and the protein signaling cascade governing the dephosphorylation of CaMKII. As previously shown, two stable states of the CaMKII phosphorylation level exist at resting intracellular calcium concentrations. Repetitive high calcium levels switch the system from a weakly- to a highly phosphorylated state (LTP). We show that the reverse transition (LTD) can be mediated by elevated phosphatase activity at intermediate calcium levels. It is shown that the CaMKII kinase-phosphatase system can qualitatively reproduce plasticity results in response to spike-timing dependent plasticity (STDP) and presynaptic stimulation protocols. A reduced model based on the CaMKII system is used to elucidate which parameters control the synaptic plasticity outcomes in response to STDP protocols, and in particular how the plasticity results depend on the differential activation of phosphatase and kinase pathways and the level of noise in the calcium transients. Our results show that the protein network including CaMKII can account for (i) induction - through LTP/LTD-like transitions - and (ii) storage - due to its bistability - of synaptic changes. The model allows to link biochemical properties of the synapse with phenomenological 'learning rules' used by theoreticians in neural network studies.
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Induction and Maintenance of Synaptic PlasticityGraupner, Michael 18 June 2008 (has links)
Synaptic long-term modifications following neuronal activation are believed to be at the origin of learning and long-term memory. Recent experiments suggest that these long-term synaptic changes are all-or-none switch-like events between discrete states of a single synapse. The biochemical network involving calcium/calmodulin-dependent protein kinase II (CaMKII) and its regulating protein signaling cascade has been hypothesized to durably maintain the synaptic state in form of a bistable switch. Furthermore, it has been shown experimentally that CaMKII and associated proteins such as protein kinase A and calcineurin are necessary for the induction of long-lasting increases (long-term potentiation, LTP) and/or long-lasting decreases (long-term depression, LTD) of synaptic efficacy. However, the biochemical mechanisms by which experimental LTP/LTD protocols lead to corresponding transitions between the two states in realistic models of such networks are still unknown. We present a detailed biochemical model of the calcium/calmodulin-dependent autophosphorylation of CaMKII and the protein signaling cascade governing the dephosphorylation of CaMKII. As previously shown, two stable states of the CaMKII phosphorylation level exist at resting intracellular calcium concentrations. Repetitive high calcium levels switch the system from a weakly- to a highly phosphorylated state (LTP). We show that the reverse transition (LTD) can be mediated by elevated phosphatase activity at intermediate calcium levels. It is shown that the CaMKII kinase-phosphatase system can qualitatively reproduce plasticity results in response to spike-timing dependent plasticity (STDP) and presynaptic stimulation protocols. A reduced model based on the CaMKII system is used to elucidate which parameters control the synaptic plasticity outcomes in response to STDP protocols, and in particular how the plasticity results depend on the differential activation of phosphatase and kinase pathways and the level of noise in the calcium transients. Our results show that the protein network including CaMKII can account for (i) induction - through LTP/LTD-like transitions - and (ii) storage - due to its bistability - of synaptic changes. The model allows to link biochemical properties of the synapse with phenomenological 'learning rules' used by theoreticians in neural network studies.
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The effects of CaMKII signaling on neuronal viabilityAshpole, Nicole M. 10 December 2013 (has links)
Indiana University-Purdue University Indianapolis (IUPUI). / Calcium/calmodulin-dependent protein kinase II (CaMKII) is a critical modulator of synaptic function, plasticity, and learning and memory. In neurons and astrocytes, CaMKII regulates cellular excitability, cytoskeletal structure, and cell metabolism. A rapid increase in CaMKII activity is observed within the first few minutes of ischemic stroke in vivo; this calcium-dependent process is also observed following glutamate stimulation in vitro. Activation of CaMKII during pathological conditions is immediately followed by inactivation and aggregation of the kinase. The extent of CaMKII inactivation is directly correlated with the extent of neuronal damage. The studies presented here show that these fluctuations in CaMKII activity are not correlated with neuronal death; rather, they play a causal role in neuronal death. Pharmacological inhibition of CaMKII in the time immediately surrounding glutamate insult protects cultured cortical neurons from excitotoxicity. Interestingly, pharmacological inhibition of CaMKII during excitotoxic insult also prevents the aggregation and prolonged inactivation of the kinase, suggesting that CaMKII activity during excitotoxic glutamate signaling is detrimental to neuronal viability because it leads to a prolonged loss of CaMKII activity, culminating in neuronal death. In support of this, CaMKII inhibition in the absence of excitotoxic insult induces cortical neuron apoptosis by dysregulating intracellular calcium homeostasis and increasing excitatory glutamate signaling. Blockade of the NMDA-receptors and enzymatic degradation of the extracellular glutamate signal affords neuroprotection from CaMKII inhibition-induced toxicity. Co-cultures of neurons and glutamate-buffering astrocytes also exhibit this slow-induced excitotoxicity, as CaMKII inhibitors reduce glutamate uptake within the astrocytes. CaMKII inhibition also dysregulates calcium homeostasis in astrocytes and leads to increased ATP release, which was neurotoxic when applied to naïve cortical neurons. Together, these findings indicate that during aberrant calcium signaling, the activation of CaMKII is toxic because it supports aggregation and prolonged inactivation of the kinase. Without CaMKII activity, neurons and astrocytes release stores of transmitters that further exacerbate neuronal toxicity.
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The role of the LAMMER kinase Kns1 and the calcium/calmodulin-dependent kinase Cmk2 in the adaptation of Saccharomyces cerevisiae to alkaline pH stressMarshall, Maria Nieves Martinez 01 February 2013 (has links)
Die LAMMER-Kinasen sind Dual-Spezifität-Proteinkinasen, die durch das namensgebende einzigartige LAMMER-Motiv gekennzeichnet sind. Sie sind evolutionär hoch konserviert und in den meisten Eukaryonten vorhanden. Die vorliegende Arbeit stellt die erste funktionelle Charakterisierung eines bisher kaum erforschten Vertreters der LAMMER-Proteinkinase Familie Kns1 aus der Bäckerhefe dar. Phänotypische Analysen belegten eine entscheidende Rolle für Kns1 in der Regulation der Toleranz gegenüber basischem pH-Stress. Das Entfernen des KNS1 Gens führte zu einer gesteigerten Empfindlichkeit der Zellen gegenüber basischen Wachstumsbedingungen. Weitere Analysen zeigten, dass Kns1 neben der katalytischen Aktivität auch nicht-katalytischen Mechanismen zur Förderung des Zellwachstums unter alkalischem pH-Stress nutzt. Die Reinigung des Kns1 Proteins in voller Länge aus E. coli ermöglichte die Identifizierung von neun in vitro-Autophosphorylierungsstellen mittels Massenspektrometrie. Die Mutation von Thr562, eine Autophosphorylierungsstelle innerhalb des LAMMER-Motivs, zu Alanin ergab in vitro eine Kinase mit intrinsischer katalytischer Aktivität, die sich jedoch in vivo hauptsächlich wie die katalytisch inaktive Kns1-Mutante verhielt. Die Calcium/Calmodulin-abhängige Proteinkinase II Cmk2, die konstitutiv autokatalytische Eigenschaften besitzt, wurde früher als mögliches in vitro Substrat von Kns1 vorgeschlagen. In dieser Arbeit beweise ich durch Verwendung einer katalytisch inaktiven Cmk2-Mutante als Substrat, dass Kns1 Cmk2 in vitro phosphoryliert. Darüber hinaus zeige ich, dass Cmk2 die basische pH-Toleranz der Zellen beschränkt. Gestützt durch genetische Hinweise agieren beide Proteine gemeinsam bei der Regulation der alkalischen Stresstoleranz, wobei Kns1 möglicherweise Cmk2 herabreguliert. Zusammenfassend beschreibt diese Arbeit eine neue und entscheidende Rolle von Kns1 und Cmk2 bei der Anpassung der Hefe an alkalisches Milieu. / The LAMMER protein kinases, termed after a unique signature motif found in their catalytic domains, are an evolutionary conserved family of dual-specificity kinases that are present in most eukaryotes. Here I report the first functional characterization of one of the most unexplored members of the LAMMER family, the budding yeast Kns1. Phenotypic analysis uncovered a crucial role for Kns1 in the control of the yeast tolerance to high pH stress. Deletion of the KNS1 gene conferred high sensitivity to alkaline pH, whereas its overexpression increased tolerance to this stress. Further analysis established that Kns1 promotes growth under alkaline pH stress using not only its catalytic activity but also non-catalytic mechanisms. Large-scale purification of full-length Kns1 from E. coli allowed for the identification of nine in vitro autophosphorylation sites on Kns1 by mass spectrometry. Mutation of the threonine residue at position 562, an autophosphorylation site located within the LAMMER motif, to a non-phosphorylatable residue yielded a kinase that preserves intrinsic catalytic activity in vitro but mostly behaves like the catalytically inactive mutant in vivo. This finding showed the physiological importance of autophosphorylation site Thr562 in the regulation of Kns1 function. The protein Cmk2, a calcium/calmodulin-dependent protein kinase II with autocatalytic properties, has been previously proposed as a possible in vitro substrate for Kns1. Here I demonstrate that Kns1 phosphorylates Cmk2 in vitro using a catalytically inactive Cmk2 mutant as substrate and show that Cmk2 restricts alkaline tolerance. Genetic evidence suggested that both proteins act in concert on a common pathway, in which Kns1 may downregulate Cmk2 to confer alkaline tolerance. In conclusion, this thesis describes a novel and crucial role for Kns1 and its in vitro substrate Cmk2 in the adaptation of yeast to alkaline stress.
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Über die differentielle Regulation von Ionenkanälen in spezifischen Nanodomänen atrialer und ventrikulärer Kardiomyozyten / Differential Regulation of Ion Channels in Specific Nanodomains of Atrial and Ventricular CardiomyocytesBrandenburg, Sören 29 June 2017 (has links)
No description available.
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