title: Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95.
abstract: Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals.
authors: Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
authors: Jun
authors: J
authors: Noritake
authors: Yuko
authors: Y
authors: Fukata
authors: Tsuyoshi
authors: T
authors: Iwanaga
authors: Naoki
authors: N
authors: Hosomi
authors: Ryouhei
authors: R
authors: Tsutsumi
authors: Naoto
authors: N
authors: Matsuda
authors: Hideki
authors: H
authors: Tani
authors: Hiroko
authors: H
authors: Iwanari
authors: Yasuhiro
authors: Y
authors: Mochizuki
authors: Tatsuhiko
authors: T
authors: Kodama
authors: Yoshiharu
authors: Y
authors: Matsuura
authors: David S
authors: DS
authors: Bredt
authors: Takao
authors: T
authors: Hamakubo
authors: Masaki
authors: M
authors: Fukata
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D020816:Amino Acid Motifs; D002451:Cell Compartmentation; D002460:Cell Line; D003712:Dendrites / Q000201:enzymology; D000076122:Disks Large Homolog 4 Protein; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D054878:Lipoylation; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism; D013347:Subcellular Fractions; D013569:Synapses / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D000123:Acetyltransferases; C062782:protein acyltransferase