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.
Fields of science
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