CALCIUM ATPASES MUTATIONS: EFFECTS ON THE SPATIO-TEMPORAL MODULATION OF CALCIUM SIGNALLING

The endoplasmic reticulum is a small structure present into our cells. It has different roles, among them it is responsible for the storing up of the calcium ion, which represent a fundamental element for the correct function of the cell. The system by which the endoplasmic reticulum accumulate calcium is due to the presence of pumps on its membrane, that utilising energy, uptake this ion from the cytosol into the compartment. When the cell received determined external stimuli, there is a release of the calcium from the reticulum into the cytosol. These changes of intracellular calcium concentration represent the most frequent manner by which the external signals are transmitted into the cell. In the last few years some genetic diseases have been described, these are characterised by severe dermatological pathologies and impairments in skeletric muscle function due to alterations of the pumps. Much remains to be learnt about these diseases, in fact the genetic defect is known but the pathways leading cellular dysfunction remain obscure. The aim of this project is to understand which are the altered mechanisms of the calcium signalling transmission into the cell. On these basis we will study the changes of calcium concentration in the cytosol and in other intracellular organelles as mitochondria both in normal and pathological cells. Since these genetic mutations could lead to other alterations, we will also analyse the morphology and distribution of the reticulum into the cells. This study, in which state of the arts approaches will be used, could highlight new information about the cellular function and it may allow the development of novel pharmacological approaches.