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Publication : Regulation of hippocampal excitatory synapses by the Zdhhc5 palmitoyl acyltransferase.

First Author  Shimell JJ Year  2021
Journal  J Cell Sci Volume  134
Issue  9 PubMed ID  33758079
Mgi Jnum  J:307374 Mgi Id  MGI:6712073
Doi  10.1242/jcs.254276 Citation  Shimell JJ, et al. (2021) Regulation of hippocampal excitatory synapses by the Zdhhc5 palmitoyl acyltransferase. J Cell Sci 134(9):jcs254276
abstractText  Palmitoylation is the most common post-translational lipid modification in the brain; however, the role of palmitoylation and palmitoylating enzymes in the nervous system remains elusive. One of these enzymes, Zdhhc5, has previously been shown to regulate synapse plasticity. Here, we report that Zdhhc5 is also essential for the formation of excitatory, but not inhibitory, synapses both in vitro and in vivo. We demonstrate in vitro that this is dependent on the enzymatic activity of Zdhhc5, its localization at the plasma membrane and its C-terminal domain, which has been shown to be truncated in a patient with schizophrenia. Loss of Zdhhc5 in mice results in a decrease in the density of excitatory hippocampal synapses accompanied by alterations in membrane capacitance and synaptic currents, consistent with an overall decrease in spine number and silent synapses. These findings reveal an important role for Zdhhc5 in the formation and/or maintenance of excitatory synapses.
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