Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95

Jun Noritake, Yuko Fukata, Tsuyoshi Iwanaga, Naoki Hosomi, Ryouhei Tsutsumi, Naoto Matsuda, Hideki Tani, Hiroko Iwanari, Yasuhiro Mochizuki, Tatsuhiko Kodama, Yoshiharu Matsuura, David S. Bredt, Takao Hamakubo, Masaki Fukata

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)

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 effi-ciently 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 (α-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.

Original languageEnglish
Pages (from-to)147-160
Number of pages14
JournalJournal of Cell Biology
Volume186
Issue number1
DOIs
Publication statusPublished - 2009 Jul 13

ASJC Scopus subject areas

  • Cell Biology

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