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UBC Theses and Dissertations

Dynamic regulation of palmitoyltransferases by synaptic activity Abazari, Danya


The formation and remodelling of synaptic contacts require the precise distribution and trafficking of proteins to specialized compartments. This dynamic trafficking of synaptic proteins is partly controlled by palmitoylation, which is the most common form of post-translational lipid modification in the brain. Notably, several studies have shown that synaptic proteins can be differentially palmitoylated in response to stress and synaptic activity. However, it is unclear how changes in synaptic activity alters protein palmitoylation. To further understand the mechanism underlying activity-induced differential palmitoylation of proteins, primary rat hippocampal cultures were used to test whether increased synaptic activity impacts transcriptional regulation or post-translational modifications of palmitoylating (zDHHCs) and depalmitoylating (ABHD17) enzymes. There were no overall changes in the transcriptional profile of the 23 DHHC enzymes nor the thioesterase, ABHD17. Post-translational modifications were not observed for zDHHC8 following increased synaptic activity. In contrast, changes were identified in the dynamic phosphorylation and/or palmitoylation of zDHHC2, zDHHC5, zDHHC6 and zDHHC9 that impact the stability or enzymatic activity of the enzymes. These modifications are likely to be important for downstream palmitoylation of synaptic proteins and the modulation of synapse plasticity.

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