title: The Sec7 guanine nucleotide exchange factor GBF1 regulates membrane recruitment of BIG1 and BIG2 guanine nucleotide exchange factors to the trans-Golgi network (TGN).
abstract: Three Sec7 guanine nucleotide exchange factors (GEFs) activate ADP-ribosylation factors (ARFs) to facilitate coating of transport vesicles within the secretory and endosomal pathways. GBF1 recruits COPI to pre-Golgi and Golgi compartments, whereas BIG1 and BIG2 recruit AP1 and GGA clathrin adaptors to the trans-Golgi network (TGN) and endosomes. Here, we report a functional cascade between these GEFs by showing that GBF1-activated ARFs (ARF4 and ARF5, but not ARF3) facilitate BIG1 and BIG2 recruitment to the TGN. We localize GBF1 ultrastructurally to the pre-Golgi, the Golgi, and also the TGN. Our findings suggest a model in which GBF1 localized within pre-Golgi and Golgi compartments mediates ARF activation to facilitate recruitment of COPI to membranes, whereas GBF1 localized at the TGN mediates ARF activation that leads to the recruitment of BIG1 and BIG2 to the TGN. Membrane-associated BIG1/2 then activates ARFs that recruit clathrin adaptors. In this cascade, an early acting GEF (GBF1) activates ARFs that mediate recruitment of late acting GEFs (BIG1/2) to coordinate coating events within the pre-Golgi/Golgi/TGN continuum. Such coordination may optimize the efficiency and/or selectivity of cargo trafficking through the compartments of the secretory pathway.
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors: Jason
authors: J
authors: Lowery
authors: Tomasz
authors: T
authors: Szul
authors: Melanie
authors: M
authors: Styers
authors: Zoe
authors: Z
authors: Holloway
authors: Viola
authors: V
authors: Oorschot
authors: Judith
authors: J
authors: Klumperman
authors: Elizabeth
authors: E
authors: Sztul
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020755:Coat Protein Complex I / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D051379:Mice; D055571:Secretory Pathway / Q000502:physiology*; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism*
chemical_list: C119087:ARFGEF1 protein, human; C119088:ARFGEF2 protein, human; C556182:Arfgef2 protein, mouse; D020755:Coat Protein Complex I; C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D020727:ADP-Ribosylation Factors; C116688:ARF4 protein, human; C571368:ARF4 protein, mouse; C116691:ARF5 protein, human; C486477:Arf5 protein, mouse
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