PT  - JOURNAL ARTICLE
AU  - Jordan J. Shimell
AU  - Andrea Globa
AU  - Marja D. Sepers
AU  - Angela R. Wild
AU  - Nusrat Matin
AU  - Lynn A. Raymond
AU  - Shernaz X. Bamji
TI  - Regulation of Hippocampal Excitatory Synapses by the Zdhhc5 Palmitoyl Acyl Transferase
AID  - 10.1101/2020.09.11.294397
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.11.294397
4099  - http://biorxiv.org/content/early/2020/09/12/2020.09.11.294397.short
4100  - http://biorxiv.org/content/early/2020/09/12/2020.09.11.294397.full
AB  - 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 Zdhhc5’s enzymatic activity, 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.