Neuronal Functions of the Drosophila DEG/ENaC Channel ppk29
Biology and Biomedical Sciences: Neurosciences
Date of Award
Doctor of Philosophy (PhD)
Chair and Committee
Degenerin/Epithelial Na+ channels (DEG/ENaC) represent a diverse family of animal-specific cation channels that play a key role in regulating ionic currents across epithelial barriers. While several family members are also enriched in the nervous system, their physiological functions in these tissues are not as well defined. To better understand the functions of DEG/ENaCs in a genetically tractable system, I used Drosophila melanogaster as a model system to investigate the function of Drosophila DEG/ENaC subunit pickpocket 29 (ppk29) in neuronal plasticity. My thesis work demonstrated that ppk29 regulates neuronal excitability via a protein-independent mechanism. By using behavioral, genetic, molecular, and neurophysiological tools I demonstrated that the 3'UTR of the ppk29 mRNA affects neuronal firing rates and associated heat-induced seizures by acting as a natural antisense transcript (NAT) that regulates the neuronal mRNA level of seizure (sei), the Drosophila homolog of the human Ether-à-go-go Related Gene (hERG) potassium channel. Surprisingly, I found that the regulatory impact of ppk29 mRNA on sei is independent of the sodium channel it encodes. Furthermore, I discovered that the PPK29 protein is required presynaptically for normal synaptic transmission at the larval neuromuscular junction (NMJ). By using genetic and neurophysiological tools, I demonstrated that PPK29 is necessary in presynaptic motor neurons for stimulus-evoked, but not spontaneous, neurotransmitter release, without an apparent impact on gross synaptic development or morphology. Additionally, my work demonstrated that PPK29 activity contributes to the modulatory effects of FMRFamide-like peptides on synaptic facilitation, suggesting this DEG/ENaC channel likely acts as important neuropeptidergic modulators in synaptic physiology. In summary, I have identified two independent mechanisms by which a single gene can affect neuronal plasticity: the first is an mRNA-dependent homeostatic response to stress; the second occurs via protein-dependent contribution to synaptic transmission and peptidergic facilitation.
Zheng, Xingguo, "Neuronal Functions of the Drosophila DEG/ENaC Channel ppk29" (2014). All Theses and Dissertations (ETDs). 1389.