title: Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter.
abstract: The Tsc1-Tsc2 complex homologous to human tuberous sclerosis complex proteins governs amino acid uptake by regulating the expression and intracellular distribution of amino acid transporters in Schizosaccharomyces pombe. Here, we performed a genetic screening for molecules that are involved in amino acid uptake and found Arn1 (also known as Any1). Arn1 is homologous to ART1, an arrestin-related trafficking adaptor (ART) in Saccharomyces cerevisiae, and contains a conserved arrestin motif, a ubiquitination site, and two PY motifs. Overexpression of arn1(+) confers canavanine resistance on cells, whereas its disruption causes hypersensitivity to canavanine. We also show that Arn1 regulates endocytosis of the Cat1 amino acid transporter. Furthermore, deletion of arn1(+) suppresses a defect of amino acid uptake and the aberrant Cat1 localization in tsc2Δ. Arn1 interacts with and is ubiquitinated by the Pub1 ubiquitin ligase, which is necessary to regulate Cat1 endocytosis. Cat1 undergoes ubiquitinations on lysine residues within the N-terminus, which are mediated, in part, by Arn1 to determine Cat1 localization. Correctively, Arn1 is an ART in S. pombe and contributes to amino acid uptake through regulating Cat1 endocytosis in which Tsc2 is involved.
authors.affiliation: Biosignal Research Center, Kobe University, Kobe 657-8501, Japan anakashima@person.kobe-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamada
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Molecular Biology Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095-1489, USA.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Tamanoi
authors.affiliation: Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
authors.forename: Ushio
authors.initials: U
authors.lastname: Kikkawa
keywords: ART; Amino acid uptake; Arn1/Any1; Arrestin-related trafficking adaptor; Endocytosis of transporter; Ubiquitination