Date of Award

1-1-2022

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

First Advisor

J. Dason

Second Advisor

B. Zielinski

Third Advisor

P. Karpowicz

Keywords

Frequenin, Calcium-binding, Proteins, Nociception

Rights

info:eu-repo/semantics/embargoedAccess

Abstract

Nociception is the sensory process that detects noxious stimuli, transduces signals, and triggers response through various ion channels and synaptic mechanisms. The calcium binding protein- Frequenin (Frq) and its mammalian homologue, Neuronal Calcium Sensor-1 (NCS-1), are important regulator of ion channels, synaptic structure, and synaptic function. Therefore, it is likely that Frq is involved in nociception, however, currently little is known about Frq’s role and its underlying mechanisms in nociception. In Drosophila, there are two frq genes, frq1and frq2, which encode proteins that are 95% identical in amino acid sequence. Here, the Drosophila larval thermal nociception model and the UV-induced tissue injury nociception sensitization model were used to gain a thorough understanding of the roles of Frq1 and Frq2 in nociception. The main findings of this thesis were: 1. Frq negatively regulates thermal nociception by regulating class IV multidendritic neuron (Drosophila nociceptors) branching. 2. Frq1 and Frq2 appear to be expressed in the class IV multidendritic neurons and in ventral nerve cord. 3. Frq2’s binding partner, Ric8a, negatively regulates nociception. 4. calpain null mutants phenocopy Frq1 and Frq2 overexpressers and demonstrate reduced nociceptive sensitivity. 5. Protective effects are found when Frq and Ric8a were overexpressed, as well as with the absence of Calpain under the UV-induced tissue injury nociception sensitization model. As the mechanisms of nociception are highly conserved between Drosophila and mammals, my data suggests that Frq/NCS-1 could represent a potential therapeutic target for pain treatment.

Available for download on Friday, May 31, 2024

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