Regulation of dendrite morphology and excitatory synapse formation by zDHHC15

2019 
Protein palmitoylation is the most common post-translational lipid modification in the brain and is mediated by a family of 23 zDHHC enzymes. There has been growing interest in zDHHCs due to mounting evidence that these enzymes play key roles in the development and function of neuronal connections and the fact that a number of zDHHCs have been associated with neurodevelopmental and neurodegenerative diseases. Loss-of-function variants in a number of zDHHCs, including zDHHC15, have been identified in patients with intellectual disabilities; however the function of zDHHC15 in the brain has not been well studied. Here we demonstrate that knocking down zDHHC15 in primary rat hippocampal cultures reduces dendritic outgrowth and arborisation as well as spine maturation. Moreover, knockdown of zDHHC15 reduces PSD-95 palmitoylation and its trafficking into dendrites, resulting in an overall decrease in the density of excitatory synapses being formed onto mutant cells.
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