Role of local palmitoylation machinery in the postsynaptic nanodomain organization

• Autorzy: Fukata M. , Yokoi N. , Fukata Y.
• Języki publikacji: EN

Abstrakty

EN

Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and palmitoyl-protein thioesterases (depalmitoylating enzymes). PSD-95 represents a major palmitoylated postsynaptic scaffolding protein that assembles various synaptic components such as AMPA- and NMDA-type glutamate receptors at the postsynaptic specialized membrane domain (postsynaptic density, PSD). Recently, we found that PSD-95 is partitioned into subsynaptic nanodomains and that PSD-95 in nanodomains undergoes continuous de/repalmitoylation cycles, thereby defining the geometry of PSDs. We found that a subset of metabolic serine hydrolases, ABHD17A, 17B and 17C, specifically depalmitoylate PSD-95 in heterologous cells. Expression of the plasma membrane-localized ABHD17 in hippocampal neurons directly binds to PSD-95 through its catalytic region and dramatically disperses PSD-95 clusters. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Uniquely, most of the PSD‑95 population undergoes rapid palmitoylation cycles. We also found that inhibition of ABHD17 expression dramatically delays the kinetics of PSD-95 depalmitoylation. We propose that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and thereby organizes the postsynaptic nanodomains. FINANCIAL SUPPORT: This work was supported by the Ministry of Education, Culture, Sports, Science and Technology (Grant numbers 15H04279, 15H01299 to Y.F; 26291045, 15H01570, 16H01371, 16K14560 to M.F.); Takeda Science Foundation to Y.F and M.F.; and The Naito Foundations to M.F.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.31-32

Twórcy

autor

Fukata M.

• National Institutes of Natural Sciences, National Institute for Physiological Sciences, Department of Molecular and Cellular Physiology, Division of Membrane Physiology, Okazaki, Japan
• SOKENDAI, The Graduate University for Advanced Studies, School of Life Science Department of Physiological Sciences, Okazaki, Japan

autor

Yokoi N.

• National Institutes of Natural Sciences, National Institute for Physiological Sciences, Department of Molecular and Cellular Physiology, Division of Membrane Physiology, Okazaki, Japan,
• SOKENDAI, The Graduate University for Advanced Studies, School of Life Science Department of Physiological Sciences, Okazaki, Japan

autor

Fukata Y.

• National Institutes of Natural Sciences, National Institute for Physiological Sciences, Department of Molecular and Cellular Physiology, Division of Membrane Physiology, Okazaki, Japan
• SOKENDAI, The Graduate University for Advanced Studies, School of Life Science Department of Physiological Sciences, Okazaki, Japan