Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain

• Published in: Nature communications Vol. 6; no. 1; p. 7840
• Main Authors: Hsu, Jia-Wei, Chen, Kuan-Jung, Lee, Fang-Jen S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.07.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 14; 38; 38/77; 42; 42/35; 631/80/641/83; 631/80/86; 82/1; 82/111; 82/29; 82/80; ADP-Ribosylation Factors - metabolism; Amino Acid Sequence; Energy Metabolism; Escherichia coli; Glucose - metabolism; Guanine Nucleotide Exchange Factors - metabolism; Humanities and Social Sciences; Membrane Glycoproteins - metabolism; Molecular Sequence Data; multidisciplinary; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - metabolism; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Yeasts
• DOI: 10.1038/ncomms8840
• ISSN: 2041-1723

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. Snf1p is the yeast homologue of AMP-activated protein kinase, a key regulator of cellular energy homeostasis. Here, Hsu et al. identify Snf1p as a non-canonical guanine nucleotide-exchange factor for the Arf3p GTPase, regulating the yeast invasive response to glucose depletion.