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

61 Citations (Scopus)

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

Fingerprint

src-Family Kinases
Golgi Apparatus
G-Protein-Coupled Receptors
Gq-G11 GTP-Binding Protein alpha Subunits
Fluxes
Membranes
Control systems
Protein folding
Heterotrimeric GTP-Binding Proteins
Protein Folding
Recycling
Endoplasmic Reticulum
Cell Cycle
Proteins
Homeostasis
Cells
KDEL receptor
Networks (circuits)

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)

Cite this

Giannotta, M., Ruggiero, C., Grossi, M., Cancino, J., Capitani, M., Pulvirenti, T., ... 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

The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi. / Giannotta, Monica; Ruggiero, Carmen; Grossi, Mauro; Cancino, Jorge; Capitani, Mirco; Pulvirenti, Teodoro; Consoli, Grazia Maria Letizia; Geraci, Corrada; Fanelli, Francesca; Luini, Alberto; Sallese, Michele.

In: EMBO Journal, Vol. 31, No. 13, 04.07.2012, p. 2869-2881.

Research output: Contribution to journalArticle

Giannotta, M, Ruggiero, C, Grossi, M, Cancino, J, Capitani, M, Pulvirenti, T, Consoli, GML, 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, vol. 31, no. 13, pp. 2869-2881. https://doi.org/10.1038/emboj.2012.134
Giannotta M, Ruggiero C, Grossi M, Cancino J, Capitani M, Pulvirenti T et al. The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi. EMBO Journal. 2012 Jul 4;31(13):2869-2881. https://doi.org/10.1038/emboj.2012.134
Giannotta, Monica ; Ruggiero, Carmen ; Grossi, Mauro ; Cancino, Jorge ; Capitani, Mirco ; Pulvirenti, Teodoro ; Consoli, Grazia Maria Letizia ; Geraci, Corrada ; Fanelli, Francesca ; Luini, Alberto ; Sallese, Michele. / The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi. In: EMBO Journal. 2012 ; Vol. 31, No. 13. pp. 2869-2881.
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