title: S-palmitoylation regulates AMPA receptors trafficking and function: a novel insight into synaptic regulation and therapeutics.
abstract: Glutamate acting on AMPA-type ionotropic glutamate receptor (AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases. In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation, and discuss how palmitoylation affects AMPA receptors function at synapses in recent years. Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China ; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, Hubei, China ; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China ; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, Hubei, China ; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
keywords: 17-ODYA, 17-octadecynoic acid; ABE, acyl-biotinyl exchange; ABP, AMPA receptor binding protein; AD, Alzheimer׳s disease; AKAP79/150, A-kinase anchoring protein 79/150; AMPA receptors; AMPAR, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; APT1, acyl-protein thioesterase-1; APT2, acyl-protein thioesterase-2; CP-AMPARs, Ca2+-permeable AMPARs; DHHC; DHHC, aspartate-histidine-histidine-cysteine; FMRP, fragile X mental retardation protein; FXS, Fragile X syndrome; GAP-43, growth associated protein-43; GRIP, glutamate receptor interacting protein; LTD, long-term depression; LTP, long-term potentiation; PATs, palmitoyl acyl transferases; PDZ, postsynaptic density-95/discs large/zona occludens-1; PICK1, protein interacting with C-kinase 1; PKA, protein kinase A; PKC, protein kinase C; PPT1, palmitoyl-protein thioesterase-1; PSD-95, postsynaptic density-95; Palmitoylation; Ras, rat sarcoma; SNAP-23, soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor protein-23; Trafficking