title: Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways.
abstract: Rab family guanosine triphosphatases (GTPases) together with their regulators define specific pathways of membrane traffic within eukaryotic cells. In this study, we have investigated which Rab GTPase-activating proteins (GAPs) can interfere with the trafficking of Shiga toxin from the cell surface to the Golgi apparatus and studied transport of the epidermal growth factor (EGF) from the cell surface to endosomes. This screen identifies 6 (EVI5, RN-tre/USP6NL, TBC1D10A-C, and TBC1D17) of 39 predicted human Rab GAPs as specific regulators of Shiga toxin but not EGF uptake. We show that Rab43 is the target of RN-tre and is required for Shiga toxin uptake. In contrast, RabGAP-5, a Rab5 GAP, was unique among the GAPs tested and reduced the uptake of EGF but not Shiga toxin. These results suggest that Shiga toxin trafficking to the Golgi is a multistep process controlled by several Rab GAPs and their target Rabs and that this process is discrete from ligand-induced EGF receptor trafficking.
authors.affiliation: Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Fuchs
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Haas
authors.forename: Robert A
authors.initials: RA
authors.lastname: Spooner
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yoshimura
authors.forename: J Michael
authors.initials: JM
authors.lastname: Lord
authors.forename: Francis A
authors.initials: FA
authors.lastname: Barr
mesh_terms: D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D021381:Protein Transport; D022621:Shiga Toxin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D004815:Epidermal Growth Factor; D020690:GTPase-Activating Proteins; D022621:Shiga Toxin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins