Identification of G Protein α Subunit-Palmitoylating Enzyme
| Autor: | Masaki Fukata, Franck Perez, Jun Noritake, Yuko Fukata, Tsuyoshi Iwanaga, Ryouhei Tsutsumi |
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| Rok vydání: | 2009 |
| Předmět: |
Gs alpha subunit
G protein Lipoylation Molecular Sequence Data Golgi Apparatus Biology Hippocampus Cell Line Receptors G-Protein-Coupled Palmitoylation Heterotrimeric G protein GTP-Binding Protein alpha Subunits Gs Humans RNA Small Interfering Molecular Biology G alpha subunit G protein-coupled receptor Neurons Base Sequence Cell Membrane Fluorescence recovery after photobleaching Articles Cell Biology Cell biology Transport protein Protein Transport Microscopy Fluorescence Gene Knockdown Techniques GTP-Binding Protein alpha Subunits Gq-G11 lipids (amino acids peptides and proteins) GTP-Binding Protein alpha Subunit Gi2 Acyltransferases Fluorescence Recovery After Photobleaching Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 29:435-447 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.01144-08 |
| Popis: | The heterotrimeric G protein alpha subunit (Galpha) 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 Galpha palmitoylating enzymes. DHHC3 and DHHC7 robustly palmitoylated Galpha(q), Galpha(s), and Galpha(i2) in HEK293T cells. Knockdown of DHHC3 and DHHC7 decreased Galpha(q/11) palmitoylation and relocalized it from the plasma membrane into the cytoplasm. Photoconversion analysis revealed that Galpha(q) 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 Galpha(q) shuttling. Furthermore, DHHC3 and DHHC7 knockdown blocked the alpha(1A)-adrenergic receptor/Galpha(q/11)-mediated signaling pathway. Together, our findings revealed that DHHC3 and DHHC7 regulate GPCR-mediated signal transduction by controlling Galpha localization to the plasma membrane. |
| Databáze: | OpenAIRE |
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