title: The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi.
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 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.
authors.affiliation: Unit of Genomic Approaches to Membrane Traffic, Department of Cellular and Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro (CH), Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Giannotta
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruggiero
authors.forename: Mauro
authors.initials: M
authors.lastname: Grossi
authors.forename: Jorge
authors.initials: J
authors.lastname: Cancino
authors.forename: Mirco
authors.initials: M
authors.lastname: Capitani
authors.forename: Teodoro
authors.initials: T
authors.lastname: Pulvirenti
authors.forename: Grazia Maria Letizia
authors.initials: GM
authors.lastname: Consoli
authors.forename: Corrada
authors.initials: C
authors.lastname: Geraci
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Michele
authors.initials: M
authors.lastname: Sallese
mesh_terms: D003198:Computer Simulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport / Q000502:physiology; D018000:Receptors, Peptide / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C064459:KDEL receptor; D018000:Receptors, Peptide; D019061:src-Family Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11