Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
J Cell Sci. 2021 May 1;134(9). doi: 10.1242/jcs.254276. Epub 2021 May 11.
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.
棕榈酰化是大脑中最常见的翻译后脂质修饰；然而，棕榈酰化和棕榈酰化酶在神经系统中的作用仍然难以捉摸。这些酶中的一种，Zdhhc5，先前已被证明可调节突触可塑性。在这里，我们报告说 Zdhhc5 对于体外和体内兴奋性突触的形成也是必不可少的，但对于抑制性突触则不是。我们在体外证明这取决于 Zdhhc5 的酶活性、其在质膜上的定位及其 C 端结构域，该结构域已在精神分裂症患者中被截断。Zdhhc5 在小鼠中的缺失导致兴奋性海马突触密度降低，同时伴随着膜电容和突触电流的改变，这与棘突数量和沉默突触的总体减少一致。这些发现揭示了 Zdhhc5 在兴奋性突触的形成和/或维持中的重要作用。
