The incredible ULKs

被引:75
作者
Alers, Sebastian [1 ]
Loeffler, Antje S. [2 ]
Wesselborg, Sebastian [2 ]
Stork, Bjoern [2 ]
机构
[1] Univ Tubingen Hosp, Dept Internal Med 1, D-72076 Tubingen, Germany
[2] Univ Hosp Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany
关键词
Atg1; Atg13; Atg17; UNC-51; EPG-1; Ulk1; Ulk2; FIP200; Atg101; Autophagy; Serine/threonine phosphorylation; ACTIVATED PROTEIN-KINASE; INHIBITS CELL-GROWTH; CAENORHABDITIS-ELEGANS; AUTOPHAGOSOME FORMATION; UNC-51-LIKE KINASE; AXONAL ELONGATION; ATG PROTEINS; RAG GTPASES; DUAL ROLE; COMPLEX;
D O I
10.1186/1478-811X-10-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Macroautophagy (commonly abbreviated as autophagy) is an evolutionary conserved lysosome-directed vesicular trafficking pathway in eukaryotic cells that mediates the lysosomal degradation of intracellular components. The cytoplasmic cargo is initially enclosed by a specific double membrane vesicle, termed the autophagosome. By this means, autophagy either helps to remove damaged organelles, long-lived proteins and protein aggregates, or serves as a recycling mechanism for molecular building blocks. Autophagy was once invented by unicellular organisms to compensate the fluctuating external supply of nutrients. In higher eukaryotes, it is strongly enhanced under various stress conditions, such as nutrient and growth factor deprivation or DNA damage. The serine/threonine kinase Atg1 was the first identified autophagy-related gene (ATG) product in yeast. The corresponding nematode homolog UNC-51, however, has additional neuronal functions. Vertebrate genomes finally encode five closely related kinases, of which UNC-51-like kinase 1 (Ulk1) and Ulk2 are both involved in the regulation of autophagy and further neuron-specific vesicular trafficking processes. This review will mainly focus on the vertebrate Ulk1/2-Atg13-FIP200 protein complex, its function in autophagy initiation, its evolutionary descent from the yeast Atg1-Atg13-Atg17 complex, as well as the additional non-autophagic functions of its components. Since the rapid nutrient-and stress-dependent cellular responses are mainly mediated by serine/threonine phosphorylation, it will summarize our current knowledge about the relevant upstream signaling pathways and the altering phosphorylation status within this complex during autophagy induction.
引用
收藏
页数:14
相关论文
共 139 条
[1]   Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction [J].
Alers, Sebastian ;
Loeffler, Antje S. ;
Paasch, Florian ;
Dieterle, Alexandra M. ;
Keppeler, Hildegard ;
Lauber, Kirsten ;
Campbell, David G. ;
Fehrenbacher, Birgit ;
Schaller, Martin ;
Wesselborg, Sebastian ;
Stork, Bjoern .
AUTOPHAGY, 2011, 7 (12) :1424-1433
[2]   Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks [J].
Alers, Sebastian ;
Loeffler, Antje S. ;
Wesselborg, Sebastian ;
Stork, Bjoern .
MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (01) :2-11
[3]   The serine/threonine kinase ULK1 is a target of multiple phosphorylation events [J].
Bach, Markus ;
Larance, Mark ;
James, David E. ;
Ramm, Georg .
BIOCHEMICAL JOURNAL, 2011, 440 :283-291
[4]   Network organization of the human autophagy system [J].
Behrends, Christian ;
Sowa, Mathew E. ;
Gygi, Steven P. ;
Harper, J. Wade .
NATURE, 2010, 466 (7302) :68-U84
[5]   RalB and the Exocyst Mediate the Cellular Starvation Response by Direct Activation of Autophagosome Assembly [J].
Bodemann, Brian O. ;
Orvedahl, Anthony ;
Cheng, Tzuling ;
Ram, Rosalyn R. ;
Ou, Yi-Hung ;
Formstecher, Etienne ;
Maiti, Mekhala ;
Hazelett, C. Clayton ;
Wauson, Eric M. ;
Balakireva, Maria ;
Camonis, Jacques H. ;
Yeaman, Charles ;
Levine, Beth ;
White, Michael A. .
CELL, 2011, 144 (02) :253-267
[6]   p53 target genes Sestrin1 and Sestrin2 connect genotoxic stress and mTOR signaling [J].
Budanov, Andrei V. ;
Karin, Michael .
CELL, 2008, 134 (03) :451-460
[7]   Evolution of Atg1 function and regulation [J].
Chan, Edmond Y. ;
Tooze, Sharon A. .
AUTOPHAGY, 2009, 5 (06) :758-765
[8]   SiRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy [J].
Chan, Edmond Y. W. ;
Kir, Serkan ;
Tooze, Sharon A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (35) :25464-25474
[9]   Kinase-Inactivated ULK Proteins Inhibit Autophagy via Their Conserved C- Terminal Domains Using an Atg13-Independent Mechanism [J].
Chan, Edmond Y. W. ;
Longatti, Andrea ;
McKnight, Nicole C. ;
Tooze, Sharon A. .
MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (01) :157-171
[10]   Autophagy takes flight in Drosophila [J].
Chang, Yu-Yun ;
Neufeld, Thomas P. .
FEBS LETTERS, 2010, 584 (07) :1342-1349