title: Selective protection of an ARF1-GTP signaling axis by a bacterial scaffold induces bidirectional trafficking arrest.
abstract: Bidirectional vesicular transport between the endoplasmic reticulum (ER) and Golgi is mediated largely by ARF and Rab GTPases, which orchestrate vesicle fission and fusion, respectively. How their activities are coordinated in order to define the successive steps of the secretory pathway and preserve traffic directionality is not well understood in part due to the scarcity of molecular tools that simultaneously target ARF and Rab signaling. Here, we take advantage of the unique scaffolding properties of E. coli secreted protein G (EspG) to describe the critical role of ARF1/Rab1 spatiotemporal coordination in vesicular transport at the ER-Golgi intermediate compartment. Structural modeling and cellular studies show that EspG induces bidirectional traffic arrest by tethering vesicles through select ARF1-GTP/effector complexes and local inactivation of Rab1. The mechanistic insights presented here establish the effectiveness of a small bacterial catalytic scaffold for studying complex processes and reveal an alternative mechanism of immune regulation by an important human pathogen.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816, USA.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Selyunin
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816, USA.
authors.forename: Lovett Evan
authors.initials: LE
authors.lastname: Reddick
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816, USA.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Weigele
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816, USA. Electronic address: neal.alto@utsouthwestern.edu.
authors.forename: Neal M
authors.initials: NM
authors.lastname: Alto
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019453:Escherichia coli O157 / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008854:Microscopy, Electron; D021381:Protein Transport; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020761:rab1 GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C429282:EspG protein, E coli; D008081:Liposomes; D011994:Recombinant Proteins; D020823:ADP-Ribosylation Factor 1; D020761:rab1 GTP-Binding Proteins