The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi

Monica Giannotta, Carmen Ruggiero, Mauro Grossi, Jorge Cancino, Mirco Capitani, Teodoro Pulvirenti, Grazia Maria Letizia Consoli, Corrada Geraci, Francesca Fanelli, Alberto Luini, Michele Sallese

Research output: Contribution to journalArticle

Abstract

Membrane trafficking involves large fluxes of cargo and membrane across separate compartments. These fluxes must be regulated by control systems to maintain homoeostasis. While control systems for other key functions such as protein folding or the cell cycle are well known, the mechanisms that control secretory transport are poorly understood. We have previously described a signalling circuit operating at the Golgi complex that regulates intra-Golgi trafficking and is initiated by the KDEL receptor (KDEL-R), a protein previously known to mediate protein recycling from the Golgi to the endoplasmic reticulum (ER). Here, we investigated the KDEL-R signalling mechanism. We show that the KDEL-R is predicted to fold like a G-protein-coupled receptor (GPCR), and that it binds and activates the heterotrimeric signalling G-protein Gαq/11 which, in turn, regulates transport through the Golgi complex. These findings reveal an unexpected GPCR-like mode of action of the KDEL-R and shed light on a core molecular control mechanism of intra-Golgi traffic.

Original languageEnglish
Pages (from-to)2869-2881
Number of pages13
JournalEMBO Journal
Volume31
Issue number13
DOIs
Publication statusPublished - Jul 4 2012

Keywords

  • endomembrane signalling
  • G-protein-coupled receptor
  • Golgi complex
  • KDEL receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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  • Cite this

    Giannotta, M., Ruggiero, C., Grossi, M., Cancino, J., Capitani, M., Pulvirenti, T., Consoli, G. M. L., Geraci, C., Fanelli, F., Luini, A., & Sallese, M. (2012). The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi. EMBO Journal, 31(13), 2869-2881. https://doi.org/10.1038/emboj.2012.134