title: Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain.
abstract: Active GTP-bound Arf GTPases promote eukaryotic cell membrane trafficking and cytoskeletal remodelling. Arf activation is accelerated by guanine nucleotide-exchange factors (GEFs) using the critical catalytic glutamate in all known Sec7 domain sequences. Yeast Arf3p, a homologue of mammalian Arf6, is required for yeast invasive responses to glucose depletion. Here we identify Snf1p as a GEF that activates Arf3p when energy is limited. SNF1 is the yeast homologue of AMP-activated protein kinase (AMPK), which is a key regulator of cellular energy homeostasis. As activation of Arf3p does not depend on the Snf1p kinase domain, assay of regulatory domain fragments yield evidence that the C-terminal hydrophobic α-helix core of Snf1p is a non-canonical GEF for Arf3p activation. Thus, our study reveals a novel mechanism for regulating cellular responses to energy deprivation, in particular invasive cell growth, through direct Arf activation by Snf1/AMPK.
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Hsu
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Kuan-Jung
authors.initials: KJ
authors.lastname: Chen
authors.affiliation: 1] Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan [2] Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Fang-Jen S
authors.initials: FJ
authors.lastname: Lee
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000595:Amino Acid Sequence; D004734:Energy Metabolism; D004926:Escherichia coli; D005947:Glucose / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C110690:FLO11 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C492128:ARF3 protein, S cerevisiae; D020727:ADP-Ribosylation Factors; D005947:Glucose