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 Galpha(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 couples to G alpha(q/11) to activate Src kinases and regulate transport through the Golgi / M., Giannotta; C., Ruggiero; M., Grossi; J., Cancino; M., Capitani; T., Pulvirenti; G. M., Consoli; C., Geraci; Fanelli, Francesca; A., Luini; M., Sallese. - In: EMBO JOURNAL. - ISSN 0261-4189. - ELETTRONICO. - 31:(2012), pp. 2869-2881. [10.1038/emboj.2012.134]

The KDEL receptor couples to G alpha(q/11) to activate Src kinases and regulate transport through the Golgi

FANELLI, Francesca;
2012

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 Galpha(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.
2012
31
2869
2881
The KDEL receptor couples to G alpha(q/11) to activate Src kinases and regulate transport through the Golgi / M., Giannotta; C., Ruggiero; M., Grossi; J., Cancino; M., Capitani; T., Pulvirenti; G. M., Consoli; C., Geraci; Fanelli, Francesca; A., Luini; M., Sallese. - In: EMBO JOURNAL. - ISSN 0261-4189. - ELETTRONICO. - 31:(2012), pp. 2869-2881. [10.1038/emboj.2012.134]
M., Giannotta; C., Ruggiero; M., Grossi; J., Cancino; M., Capitani; T., Pulvirenti; G. M., Consoli; C., Geraci; Fanelli, Francesca; A., Luini; M., Sallese
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/747341
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