Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes

被引:593
作者
Young, Andrew R. J.
Chan, Edmond Y. W.
Hu, Xiao Wen
Koch, Robert
Crawshaw, Samuel G.
High, Stephen
Hailey, Dale W.
Lippincott-Schwartz, Jennifer
Tooze, Sharon A.
机构
[1] Canc Res UK, London Res Inst, London WC2A 3PX, England
[2] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England
[3] NICHD, CBMB, NIH, Bethesda, MD 20892 USA
关键词
autophagy; Golgi; Rab proteins; intracellular transport; transmembrane protein;
D O I
10.1242/jcs.03172
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Autophagy, fundamentally a lysosomal degradation pathway, functions in cells during normal growth and certain pathological conditions, including starvation, to maintain homeostasis. Autophagosomes are formed through a mechanism that is not well understood, despite the identification of many genes required for autophagy. We have studied the mammalian homologue of Atg9p, a multi-spanning transmembrane protein essential in yeast for autophagy, to gain a better understanding of the function of this ubiquitious protein. We show that both the N- and C-termini of mammalian Atg9 (mAtg9) are cytosolic, and predict that mAtg9 spans the membrane six times. We find that mAtg9 is located in the trans-Golgi network and late endosomes and colocalizes with TGN46, the cation-independent mannose-6-phosphate receptor, Rab7 and Rab9. Amino acid starvation or rapamycin treatment, which upregulates autophagy, causes a redistribution of mAtg9 from the TGN to peripheral, endosomal membranes, which are positive for the autophagosomal marker GFP-LC3. siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution. The redistribution of mAtg9 also requires PI 3-kinase activity, and is reversed after restoration of amino acids. We speculate that starvation-induced autophagy, which requires mAtg9, may rely on an alteration of the steady-state trafficking of mAtg9, in a Atg1-dependent manner.
引用
收藏
页码:3888 / 3900
页数:13
相关论文
共 55 条
  • [1] Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells
    Barbero, P
    Bittova, L
    Pfeffer, SR
    [J]. JOURNAL OF CELL BIOLOGY, 2002, 156 (03) : 511 - 518
  • [2] Autophagy and the cytoplasm to vacuole targeting pathway both require Aut10p
    Barth, H
    Meiling-Wesse, K
    Epple, UD
    Thumm, M
    [J]. FEBS LETTERS, 2001, 508 (01) : 23 - 28
  • [3] The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes
    Blommaart, EFC
    Krause, U
    Schellens, JPM
    VreelingSindelarova, H
    Meijer, AJ
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 243 (1-2): : 240 - 246
  • [4] Signals for sorting of transmembrane proteins to endosomes and lysosomes
    Bonifacino, JS
    Traub, LM
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2003, 72 : 395 - 447
  • [5] PpATG9 encodes a novel membrane protein that traffics to vacuolar membranes, which sequester peroxisomes during pexophagy in Pichia pastoris
    Chang, T
    Schroder, LA
    Thomson, JM
    Klocman, AS
    Tomasini, AJ
    Stromhaug, PE
    Dunn, WA
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2005, 16 (10) : 4941 - 4953
  • [6] A misassembled transmembrane domain of a polytopic protein associates with signal peptide peptidase
    Crawshaw, SG
    Martoglio, B
    Meacock, SL
    High, S
    [J]. BIOCHEMICAL JOURNAL, 2004, 384 : 9 - 17
  • [7] Dittié AS, 1999, J CELL SCI, V112, P3955
  • [9] ELLIS JA, 1992, PROTEIN TARGETING PR, P25
  • [10] STUDIES ON INDUCED CELLULAR AUTOPHAGY .2. CHARACTERIZATION OF MEMBRANES BORDERING AUTOPHAGOSOMES IN PARENCHYMAL LIVER CELLS
    ERICSSON, JL
    [J]. EXPERIMENTAL CELL RESEARCH, 1969, 56 (2-3) : 393 - +