Date of Award

10-11-2024

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Supervisor

Jeffrey Dason

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Phosphatidylserine (PS) is a membrane lipid that has been implicated in various neuronal processes such as synaptic development, neurotransmission, and vesicle cycling. PS is synthesized by Phosphatidylserine synthase (Pss) and upon localization to the plasma membrane is translocated from the outer to inner leaflet by the phospholipid flippase ATP8B. Knockdown of Drosophila glial-Pss has been shown to reduce synaptogenesis/axonal growth. The effects of loss of ATP8B on synaptic growth and plasticity have not been characterized. The primary objective of this thesis was to determine if PS is required for normal levels of synaptic growth and plasticity. Initial experiments involved determining if PS is present at the neuromuscular junction (NMJ). Using the PS biosensor Lactadherin-C2, PS was visibly present in motor neurons, glia, and muscle at the NMJ. ATP8B and Pss mutants were then utilized to study the role of PS in normal synaptic growth. Compared to its control, a Pss mutant exhibited a reduction in bouton abundance suggesting that PS is required for normal synaptic development. Next, ATP8B mutants were reared at 23°C and 30°C to study a type of synaptic plasticity known as activity-dependent synaptic growth which is induced at increased temperatures. Reduced ATP8B impaired this activity-dependent synaptic growth when reared at 30°C. Finally, using this same assay, knockdown of glial-Pss was found to impair activity-dependent synaptic growth. Overall, these findings show that PS is present at the Drosophila NMJ and is required for proper synaptic development and plasticity.

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