Identification of G protein a subunit-palmitoylating enzyme

Ryouhei Tsutsumi, Yuko Fukata, Jun Noritake, Tsuyoshi Iwanaga, Franck Perez, Masaki Fukata

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

The heterotrimeric G protein α subunit (Gα) is targeted to the cytoplasmic face of the plasma membrane through reversible lipid palmitoylation and relays signals from G-protein-coupled receptors (GPCRs) to its effectors. By screening 23 DHHC motif (Asp-His-His-Cys) palmitoyl acyl- transferases, we identified DHHC3 and DHHC7 as Gα palmitoylating enzymes. DHHC3 and DHHC7 robustly palmitoylated Gαq,Gαq, and Gαi2 in HEK293T cells. Knockdown of DHHC3 and DHHC7 decreased Gαq/11 palmitoylation and relocalized it from the plasma membrane into the cytoplasm. Photoconversion analysis revealed that Gαq rapidly shuttles between the plasma membrane and the Golgi apparatus, where DHHC3 specifically localizes. Fluorescence recovery after photobleaching studies showed that DHHC3 and DHHC7 are necessary for this continuous Gαq shuttling. Furthermore, DHHC3 and DHHC7 knockdown blocked the α1A-adrenergic receptor/Gα q/11-mediated signaling pathway. Together, our findings revealed that DHHC3 and DHHC7 regulate GPCR-mediated signal transduction by controlling Gα localization to the plasma membrane.

Original languageEnglish
Pages (from-to)435-447
Number of pages13
JournalMolecular and cellular biology
Volume29
Issue number2
DOIs
Publication statusPublished - 2009 Jan

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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