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Identifier 000435543
Title The implication of DEL-4, an ENaC/DEG protein family member, in neuronal activity and acid sensation
Alternative Title Ο ρόλος της πρωτεΐνης DEL-4, μέλος της οικογένειας καναλιών ENaC/DEG, στην φυσιολογική λειτουργία των νευρώνων και την αντίληψη όξινου περιβάλλοντος
Author Γκικολάϊ, Μάρθα
Thesis advisor Ταβερναράκης, Νεκτάριος
Reviewer Καρδάσης, Δημήτριος
Μπερτσιάς, Γεώργιος
Abstract DEL-4, a sodium channel present in C. elegans neuronal cells, is a member of a broad and diverse protein family, the DEG/ENaC. The properties of this channel appear to differ from the rest identified members of this family. A constitutively active gate, generating inward sodium current possibly exerts a regulatory role in neuronal transmission since it rapidly closes under low pH. From an in silico analysis, it was found that del-4 promoter possesses binding sites for DAF-16, SKN-1 and HSF-1 transcriptions factors. These three factors are the primary regulators of starvation, oxidative stress and heat stress responses, respectively. Collectively, we hypothesize that DEL-4 participates in sensory integration, modulating neurotransmission. From aldicarb behavioural assay and conducted experiments of the lab, involving dopaminergic signalling and locomotion, we come to support the notion that DEL-4 indeed alters physiological synaptic release. To get a more comprehensive look of how a normal or disrupted DEL-4 channel affects neuronal function, we used a voltage sensor expressed in dopaminergic neurons. The observation was that in both mutant and a stress induction cases, the cell membrane was becoming hyperpolarized. Notably, we also checked if the malfunctioning channel alters the integrity of the neurons. We noticed increased neurodegeneration events in mutants and intriguingly a more neuroprotective effect of DEL-4 overexpression. Our results provide new insights into how sodium channels participate in the mechanism of neuronal integration.
Language English
Subject Όξινο περιβάλλον
Κανάλια νατρίου
Νηματώδης σκώληκας
Issue date 2020-12-17
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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