title: Four GTPases differentially regulate the Sec7 Arf-GEF to direct traffic at the trans-golgi network.
abstract: Traffic through the Golgi complex is controlled by small GTPases of the Arf and Rab families. Guanine nucleotide exchange factor (GEF) proteins activate these GTPases to control Golgi function, yet the full assortment of signals regulating these GEFs is unknown. The Golgi Arf-GEF Sec7 and the homologous BIG1/2 proteins are effectors of the Arf1 and Arl1 GTPases. We demonstrate that Sec7 is also an effector of two Rab GTPases, Ypt1 (Rab1) and Ypt31/32 (Rab11), signifying unprecedented signaling crosstalk between GTPase pathways. The molecular basis for the role of Ypt31/32 and Rab11 in vesicle formation has remained elusive. We find that Arf1, Arl1, and Ypt1 primarily affect the membrane localization of Sec7, whereas Ypt31/32 exerts a dramatic stimulatory effect on the nucleotide exchange activity of Sec7. The convergence of multiple signaling pathways on a master regulator reveals a mechanism for balancing incoming and outgoing traffic at the Golgi.
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: McDonold
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address: jcf14@cornell.edu.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Fromme
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D029701:Saccharomyces cerevisiae Proteins; C066755:Sec7 guanine nucleotide exchange factors; D033921:Vesicular Transport Proteins; C087905:YPT31 protein, S cerevisiae; C487039:ARL1 protein, S cerevisiae; C060755:YPT1 protein, S cerevisiae; C121633:YPT32 protein, S cerevisiae; D020823:ADP-Ribosylation Factor 1; D020559:Monomeric GTP-Binding Proteins; D020691:rab GTP-Binding Proteins