RGD Reference Report - Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95. - Rat Genome Database

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

Authors: Noritake, Jun  Fukata, Yuko  Iwanaga, Tsuyoshi  Hosomi, Naoki  Tsutsumi, Ryouhei  Matsuda, Naoto  Tani, Hideki  Iwanari, Hiroko  Mochizuki, Yasuhiro  Kodama, Tatsuhiko  Matsuura, Yoshiharu  Bredt, David S  Hamakubo, Takao  Fukata, Masaki 
Citation: Noritake J, etal., J Cell Biol. 2009 Jul 13;186(1):147-60. doi: 10.1083/jcb.200903101.
RGD ID: 21201259
Pubmed: (View Article at PubMed) PMID:19596852
DOI: Full-text: DOI:10.1083/jcb.200903101

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.

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Dlg4  (discs large MAGUK scaffold protein 4)
Zdhhc2  (zinc finger DHHC-type palmitoyltransferase 2)
Zdhhc3  (zinc finger DHHC-type palmitoyltransferase 3)

Additional Information