Comparative analysis of palmitoylation sites of serotonin (5‐HT) receptors in vertebrates

Abstract

Our findings mean that dynamic regulation of 5-HT receptors made possible by reversible post-translational protein palmitoylation may be critical for refined functions of the vertebrate serotonergic systems.

Post‐translational palmitoylation of ionotropic glutamate receptors in excitatory synaptic functions

“…There are also two distinct palmitoylation clusters in the NMDA receptor (right). Palmitoylated cysteine residues in the C-terminal region of GluN2A and GluN2B Suppiramaniam, & Wooten, 2006;Lu & Roche, 2012;Lussier, Sanz-Clemente, & Roche, 2015;Parkinson & Hanley, 2018). Many studies have shown that the post-translational protein modifications, such as phosphorylation of AMPA receptor subunits, play critical roles in the regulation of synaptic plasticity, such as LTP (Barria, Muller, Derkach, Griffith, & Soderling, 1997;Buonarati, Hammes, Watson, Greger, & Hell, 2019;Lee et al, 2003;Lee, Barbarosie, Kameyama, Bear, & Huganir, 2000), long-term depression (Chung, Steinberg, Huganir, & Linden, 2003;Lee et al, 2000;Lee, Kameyama, Huganir, & Bear, 1998;Steinberg et al, 2006), homeostatic scaling (Hayashi, Umemori, Mishima, & Yamamoto, 1999;Hayashi & Huganir, 2004;Hu et al, 2010;Yong et al, 2020), and hyperexcitability (Rakhade et al, 2008;Rakhade et al, 2012).…”

“…Generally, post‐translational palmitoylation acts as a sticky tag that can direct proteins, including many neuronal receptors and ion channels, to specific regions of the plasma membrane, or specific intracellular membranes or vesicles. Many neuronal receptors and ion channels are reversibly palmitoylated and de‐palmitoylated in the regulation of protein functions and their targeting to membranes and synapses (Borroni, Valles, & Barrantes, 2016; Hayashi, 2017; Itoh, Kaizuka, & Hayashi, 2017; Kaizuka & Hayashi, 2018; Kang et al, 2008; Shipston, 2011).…”

“…In these neurophysiological processes, AMPA receptors trafficking to and from synapses are dynamically regulated by posttranslational protein modifications (Anggono & Huganir, 2012;Jiang, F I G U R E 1 Classification of ionotropic glutamate receptors (iGluRs). In the upper part of the Figure, iGluR subunits in AMPA-type (AMPA receptor), KA-type (KA receptor), δ-type (δ receptor), and NMDA-type (NMDA receptor).…”

“…An arrow indicates conserved cysteine residues, and arrowheads indicate additional cysteine residues. Dotted box indicates 4.1N binding motif in GluA1 GluA1, Ca 2+ /calmodulin-dependent protein kinase II-mediated phosphorylation at S831 is increased by LTP induction (Derkach et al, 2007;Jiang et al, 2006;Kessels & Malinow, 2009;Lussier et al, 2015;Shepherd & Huganir, 2007). Furthermore, GluA1 palmitoylation suppressed excessive spine enlargement above a certain size after LTP (Holtmaat & Svoboda, 2009; Kasai, Fukuda, Watanabe, Hayashi-Takagi, & Noguchi, 2010;Matsuzaki et al, 2001;Matsuzaki, Honkura, Ellis-Davies, & Kasai, 2004).…”

Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders

“…Mice are currently thought to have five [ 64 ] and rats four isoforms, with the fourth, (c1) isoform expressed in the gastrointestinal tract [ 59 , 63 ]. In rat brain, no significant difference in expression between the long and short variants has been found by ISH [ 65 ].…”