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In the mammalian CNS, glutamate is the major excitatory neurotransmitter. Ionotropic glutamate receptors (iGluRs) are responsible for the glutamate-mediated postsynaptic excitation of neurons. Regulation of glutamatergic synapses is critical for higher brain functions including neural communication, memory formation, learning, emotion, and behaviour. Many previous studies have shown that post-translational protein S-palmitoylation, the only reversible covalent attachment of lipid to protein, regulates synaptic expression, intracellular localization, and membrane trafficking of iGluRs and their scaffolding proteins in neurons. This modification mechanism is extremely conserved in the vertebrate lineages. The failure of appropriate palmitoylation-dependent regulation of iGluRs leads to hyperexcitability that reduces the maintenance of network stability, resulting in brain disorders, such as epileptic seizures. This review summarizes advances in the study of palmitoylation of iGluRs, especially AMPA receptors and NMDA receptors, and describes the current understanding of palmitoylation-dependent regulation of excitatory glutamatergic synapses. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.4/issuetoc. [ABSTRACT FROM AUTHOR]

Among major histological subtypes of epithelial ovarian cancer, a higher incidence of ovarian clear cell carcinoma (OCCC) is observed in East Asian populations, particularly in Japan. Despite recent progress in the immune checkpoint inhibitors for a wide variety of cancer cell types, patients with OCCC exhibit considerably low response rates to these drugs. Hence, urgent efforts are needed to develop a novel immunotherapeutic approach for OCCC. CD47, a transmembrane protein, is overexpressed in almost all cancer cells and disrupts macrophage phagocytic activity in cancer cells. Ezrin-Radixin-Moesin (ERM) family member of proteins serve as scaffold proteins by crosslinking certain transmembrane proteins with the actin cytoskeleton, contributing to their plasma membrane localization. Here, we examined the role of ERM family in the plasma membrane localization and functionality of CD47 in OCCC cell lines derived from Japanese women. Confocal laser scanning microscopy analysis showed colocalization of CD47 with all three ERM in the plasma membrane of OCCC cells. RNA interference-mediated gene silencing of moesin, but not others, decreased the plasma membrane expression and immune checkpoint function of CD47, as determined by flow cytometry and in vitro phagocytosis assay using human macrophage-like cells, respectively. Interestingly, clinical database analysis indicated that moesin expression in OCCC was higher than that in other histological subtypes of ovarian cancers, and the expression of CD47 and moesin increased with the cancer stage. In conclusion, moesin is overexpressed in OCCC and may be the predominant scaffold protein responsible for CD47 plasma membrane localization and function in OCCC. [Display omitted] • Moesin was overexpressed in the ovarian clear cell carcinoma common in Japanese. • Moesin highly co-localizes and interacts with innate immune checkpoint CD47. • Moesin contributes to the macrophage checkpoint function of CD47. [ABSTRACT FROM AUTHOR]