AstroSignals · Spatiotemporal dynamics of subcellular energy metabolism in astrocytes
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2015-04-01 → 2017-03-31
- Финансиране от ЕС
- 183 455 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Астроцитите в човешкия мозък се изследват, за да се установи дали енергията (ATP) се разпределя локално в микрозони, вместо в общ обем. Това помага да се разбере как тези клетки захранват невроните и регулират сигналите в мозъка.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Spatiotemporal dynamics of subcellular energy metabolism in astrocytes
Subcellular compartmentalization of signal transduction is of critical importance for cellular function. Second messenger molecules within cells, such as calcium, activate or inhibit multiple targets, and it's only through the spatial and temporal compartmentalization of these messengers into microdomains that specificity and versatility of signal transduction is made possible. Thereby, instead of a global activation of all its subcellular targets, a second messenger activates only the targets that are within its microdomain. While it is well established that signal transduction inside cells in spatially and temporally compartmentalized, there remains a widespread assumption that the metabolic pathways providing energy, in the form of ATP, for sub-cellular signal transduction are not compartmentalized, but merely feed a global cellular pool of ATP. The overall objectives of this project are to compile and critically review the current evidence for sub-cellular compartmentalization of energy metabolism, and to establish experimentally whether we can find evidence for such compartmentalization in human astrocytes, the most abundant type of cell in the human brain. As a related issue, we developed a hypothesis of a novel pathway for subcellular glucose compartmentalization inside astrocytes. This pathway could explain the very efficient glucose uptake into these cells and facilitate astrocytic provision of metabolic support for neurons, one of the most important functions of astrocytes. An additional objective therefore is to experimentally test this hypothesis. Combining state-of-the-art techniques and expertise in the fields of cell signalling and metabolism, the results of this project enhance our understanding of metabolic regulation of signal transduction. A deeper understanding of the organization of subcellular energy metabolism and it's regulation of signalling may in the future open new possibilities for targeted treatments of brain diseases.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The functional significance of subcellular compartmentalization in signal transduction has emerged in recent years, a development that is gaining momentum due to significant advances in optical microscopy and genetically encoded biosensors. However, much less attention has been given to the spatial architecture of the metabolic networks that provide energetic support for intracellular processes. This project will investigate spatiotemporal organization of energy metabolism in astrocytes, focusing on two hypotheses:• I propose that within astrocytes, signalling microdomains are energetically supported by local delivery of ATP. I will employ confocal and total internal reflection fluorescence (TIRF) microscopy, using biosensors for ATP, glucose and Ca2+ that can be targeted to subcellular locations. My initial focus is on cultured human astrocytes and the provision of ATP for Ca2+ signalling. Do the five cellular sources of astrocytic ATP support different ATP pools? Which pools are needed for the many ATP-requiring steps that link cell-surface receptors to Ca2+ signals?• I suggest that the ER lumen may provide a glucose reservoir that allows rapid intracellular transfer of glucose to meet local energy needs. The ER of astrocytes contains luminal glucose-6-phosphatase-β (G-6-Pase-β) and a glucose-6-phosphate transporter, which together can generate an ER luminal pool of glucose. The source of glucose-6-phosphate transported into the ER and the function of luminal glucose are unknown. Using cytosolic and ER-targeted glucose sensors, immunocytochemistry and siRNA knockdown of glucose G-6-Pase-β, I will determine the source of the glucose pool and whether it contributes to metabolic support of Ca2+ signals.Combining state-of-the-art techniques and expertise in the fields of cell signalling and metabolism, this project will enhance our understanding of metabolic regulation of signal transduction, opening new possibilities for targeted treatments of brain diseases.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз