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

• Published in: The EMBO journal 2012-06, Vol.31 (13), p.2869-2881
• Main Authors: Giannotta, Monica, Ruggiero, Carmen, Grossi, Mauro, Cancino, Jorge, Capitani, Mirco, Pulvirenti, Teodoro, Consoli, Grazia Maria Letizia, Geraci, Corrada, Fanelli, Francesca, Luini, Alberto, Sallese, Michele
• Format: Article
• Language: English
• Subjects: Computer Simulation; EMBO20; EMBO37; endomembrane signalling; Endoplasmic Reticulum - metabolism; G-protein-coupled receptor; Golgi Apparatus - metabolism; Golgi complex; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; HeLa Cells; Humans; KDEL receptor; Protein Transport - physiology; Receptors, Peptide - metabolism; Signal Transduction - physiology; src-Family Kinases - metabolism
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2012.134

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 Gα q/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. The KDEL receptor regulates intra‐Golgi trafficking homoeostasis via a cargo fluxdriven signalling pathway. This study reveals that KDEL‐R, which is predicted to resemble a G‐protein‐coupled receptor, activates the heterotrimeric signalling G‐protein G[α]q/1 at the Golgi membrane.