CALCIUM_NEURONS · New intracellular calcium stores and apoptosis mechanisms in neurons
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-04-15 → 2006-04-14
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - CALCIUM_NEURONS (New intracellular calcium stores and apoptosis mechanisms in neurons)
Increases in the intracellular Ca2+ concentration represent a ubiquitous transduction mechanism involved in a diverse range of cellular processes from fertilisation to programmed cell death (apoptosis). Three intracellular organelles are thought to play a crucial role in apoptosis: the endoplasmatic reticulum (ER), the mitochondria and more recently the lysosomes. Conversely, the ER and the mitochondria are regarded as the main intracellular Ca2+ stores and/or sinks. We have recently uncovered that acidic lysosomal-related organelles acts as intracellular Ca2+ stores from which stimuli-induced NAADP can release Ca2+. Our 5-year research project focused on 1) extending the universality of acidic lysosomal-like organelles as intracellular Ca2+ stores to hippocampal neurons, and 2) exploring the intriguing theory that lysosomal membrane permeability observed in apoptosis can be a result of disruption of the lysosomal Ca2+ homeostasis and Ca2+ dynamics between different intracellular stores. During the first year of the project and thanks to the funding from a European Reintegration Grant and the collaboration with Dr. Churchill and Dr. Galione (University of Oxford), we set up different novel protocols and state-of-art techniques to achieve our objectives. Among the most relevant techniques, we can name Calcium Imaging, microinjection of caged compounds and subsequent activation by photolysis, synthesis of caged NAADP and [32P]NAADP, HPLC purification of nucleotides such as NADP, NADPH and NAADP and detection of cathepsin released to the cytosol. Our preliminary results show that NAADP delivered intracellularly but not exogenously can release intracellular calcium in hippocampal neurons. Further work in the next following 4 years of the project is needed to understand this novel signalling pathway and its implication in apoptosis of neurons from hippocampus.
Data: CORDIS, © European Union
Project objective
In order to maintain fidelity between a given stimulus and its own unique downstream physiological response, cells have elaborated stimulus-specific networks of intracellular signalling cascades, even within the same cell. In this context of agonist specificity, it has become clear that release of calcium from intracellular stores is a primary governing factor.Moreover, intracellular calcium stores are key and active participants in important physiological processes such apoptosis of a variety of cells. The endoplasmatic reticulum (ER) related stores and mitochondria have been long regarded as the main intracellular stores and/or calcium sinks, however recent publications demonstrated that intracellular acid lysosomal-like organelles act as novel and unique intracellular calcium stores in sea urchin eggs and pancreatic cells.More importantly, these lysosomal related compartments are involved in specific physiological responses. Here I propose a research project that aims to extend the universality of acidic calcium stores to neurons and look into its physiological implications.The specific objectives are:- to investigate if the intracellular acidic organelles can act as a calcium stores selectively recruited by extracellular stimuli in neurons; and- to explore the importance of calcium dynamics between intracellular calcium stores and disruption of lysosomal calcium homeostasis in apoptosis, an important physiological process where lysosomes have been shown to play a key role.State-of-the-art technology and innovative protocols will be used to carry out this project. The knowledge gained will lead to new insights into the signalling mechanisms of nervous system and to novel neuroprotective strategies interfering in the calcium homeostasis. Therefore, it w ill enable the discovery of new pharmacological targets for neurodegenerative processes.
Original text from CORDIS.
Participants
- UNIVERSITAT AUTONOMA DE BARCELONA · BELLATERRA (CERDANYOLA DEL VALLES)CoordinatorSpain
Links
Data: CORDIS, © European Union