Store-operated calcium entry in neural cells. A role in Charcot-Marie-Tooth disease
Author
González Sánchez, PalomaEntity
UAM. Departamento de Biología Molecular; Centro de Biología Molecular Severo OchoaDate
2017-09-22Subjects
Dientes - Enfermedades - Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 22-09-2017Esta tesis tiene embargado el acceso al texto completo hasta el 22-09-2019
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Calcium (Ca2+) is a universal second messenger in eukaryotic cells that regulates numerous
cellular processes. Cells have developed highly specific mechanisms to control the concentration
of Ca2+ in each cellular location. The store-operated calcium entry (SOCE) is a mechanism that
allows Ca2+ influx from the external medium into the cytosol when the ER-Ca2+ levels decrease,
being one of its functions the replenishment of intracellular Ca2+ stores. We have addressed the
role of SOCE in different neural cells, neuroblastoma cells and primary mouse cortical neurons.
In neuroblastoma cells, we have found that SOCE activity is facilitated by mitochondrial Ca2+
uptake, preventing its Ca2+-dependent inactivation and Ca2+ entry through SOC channels impacts
on cell metabolism, stimulating mitochondrial respiration. SOCE-driven Ca2+ entry and SOCEstimulated
respiration were impaired in a cellular model of Charcot-Marie-Tooth disease caused
by GDAP1 gene, suggesting that a failure in bioenergetics may be a pathological mechanism
involved in the disease. In neurons, the existence of SOCE pathway is under debate, but we have
found that SOCE takes place in cortical neurons, although contrary to findings in neuroblastoma
cell lines, it is not modulated by Ca2+ uptake into mitochondria. Moreover, we have investigated
the role of neuronal SOCE in the response to physiological stimuli which have the ability to
mobilize Ca2+ from intracellular stores, and we found that SOCE is involved in both mAChRs
and mGluRs function: a) SOCE plays a role in muscarinic-enhanced spontaneous Ca2+ oscillations
and the subsequent stimulation of mitochondrial respiration; and b) SOCE is required for the
response to the mGluRs I agonist DHPG, to maintain cytosolic Ca2+ and develop DHPG-LTD.
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