RRC ID 22767
Author Nakase Y, Nakase M, Kashiwazaki J, Murai T, Otsubo Y, Mabuchi I, Yamamoto M, Takegawa K, Matsumoto T.
Title The fission yeast β-arrestin-like protein Any1 is involved in TSC-Rheb signaling and the regulation of amino acid transporters.
Journal J Cell Sci
Abstract Rheb GTPase and the Tsc1-Tsc2 protein complex, which serves as a GTPase-activating protein for Rheb, have crucial roles in the regulation of cell growth in response to extracellular conditions. In Schizosaccharomyces pombe, Rheb and Tsc1-Tsc2 regulate cell cycle progression, the onset of meiosis and the uptake of amino acids. In cells lacking Tsc2 (Δtsc2), the amino acid transporter Aat1, which is normally expressed on the plasma membrane under starvation conditions, is confined to the Golgi. Here, we show that the loss of either pub1(+), encoding an E3 ubiquitin ligase, or any1(+), encoding a β-arrestin-like protein, allows constitutive expression of Aat1 on the plasma membrane in Δtsc2 cells, suggesting that Pub1 and Any1 are required for localization of Aat1 to the Golgi. Subsequent analysis revealed that, in the Golgi, Pub1 and Any1 form a complex that ubiquitylates Aat1. Physical interaction of Pub1 and Any1 is more stable in Δtsc2 cells than in wild-type cells and is independent of Tor2 activity. These results indicate that the TSC-Rheb signaling pathway regulates the localization of amino acid transporters via Pub1 and Any1 in a Tor2-independent manner. Our study demonstrates that, unlike in budding yeast (in which Rsp5 and ARTs, a pair of proteins analogous to Pub1 and Any1, respectively, primarily act to reduce expression of the transporters on plasma membrane when nutrients are abundant), the primary role of fission yeast Pub1 and Any1 is to store the transporter in the Golgi under nutrient-rich conditions.
Volume 126(Pt 17)
Pages 3972-81
Published 2013-9-1
DOI 10.1242/jcs.128355
PII jcs.128355
PMID 23813957
MeSH Amino Acid Transport Systems, Basic / biosynthesis Amino Acid Transport Systems, Basic / metabolism Arrestins / deficiency Arrestins / genetics Arrestins / metabolism* Carbon-Nitrogen Ligases / deficiency Carbon-Nitrogen Ligases / genetics Carbon-Nitrogen Ligases / metabolism* Cell Cycle Cell Membrane / metabolism Golgi Apparatus / metabolism Meiosis Monomeric GTP-Binding Proteins / metabolism* Multiprotein Complexes / metabolism Phosphatidylinositol 3-Kinases / metabolism Schizosaccharomyces Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction beta-Arrestins
IF 4.573
Times Cited 14
Yeast FY7683