Universität zu Köln

Kraft, Claudine, Kijanska, Monika, Kalie, Eyal, Siergiejuk, Edyta, Lee, Sung Sik ORCID: 0000-0001-9267-232X, Semplicio, Giuseppe, Stoffel, Ingrid, Brezovich, Andrea, Verma, Mayanka, Hansmann, Isabella, Ammerer, Gustav, Hofmann, Kay, Tooze, Sharon ORCID: 0000-0002-2182-3116 and Peter, Matthias ORCID: 0000-0002-2160-6824 (2012). Binding of the Atg1/ULK1 kinase to the ubiquitin-like protein Atg8 regulates autophagy. Embo J., 31 (18). S. 3691 - 3704. HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

Autophagy is an intracellular trafficking pathway sequestering cytoplasm and delivering excess and damaged cargo to the vacuole for degradation. The Atg1/ULK1 kinase is an essential component of the core autophagy machinery possibly activated by binding to Atg13 upon starvation. Indeed, we found that Atg13 directly binds Atg1, and specific Atg13 mutations abolishing this interaction interfere with Atg1 function in vivo. Surprisingly, Atg13 binding to Atg1 is constitutive and not altered by nutrient conditions or treatment with the Target of rapamycin complex 1 (TORC1)-inhibitor rapamycin. We identify Atg8 as a novel regulator of Atg1/ULK1, which directly binds Atg1/ULK1 in a LC3-interaction region (LIR)-dependent manner. Molecular analysis revealed that Atg13 and Atg8 cooperate at different steps to regulate Atg1 function. Atg8 targets Atg1/ULK1 to autophagosomes, where it may promote autophagosome maturation and/or fusion with vacuoles/lysosomes. Moreover, Atg8 binding triggers vacuolar degradation of the Atg1-Atg13 complex in yeast, thereby coupling Atg1 activity to autophagic flux. Together, these findings define a conserved step in autophagy regulation in yeast and mammals and expand the known functions of LIR-dependent Atg8 targets to include spatial regulation of the Atg1/ULK1 kinase. The EMBO Journal (2012) 31, 3691-3703. doi:10.1038/emboj.2012.225; Published online 10 August 2012

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kraft, Claudine UNSPECIFIED UNSPECIFIED UNSPECIFIED Kijanska, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalie, Eyal UNSPECIFIED UNSPECIFIED UNSPECIFIED Siergiejuk, Edyta UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Sung Sik UNSPECIFIED orcid.org/0000-0001-9267-232X UNSPECIFIED Semplicio, Giuseppe UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoffel, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Brezovich, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Verma, Mayanka UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansmann, Isabella UNSPECIFIED UNSPECIFIED UNSPECIFIED Ammerer, Gustav UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED UNSPECIFIED UNSPECIFIED Tooze, Sharon UNSPECIFIED orcid.org/0000-0002-2182-3116 UNSPECIFIED Peter, Matthias UNSPECIFIED orcid.org/0000-0002-2160-6824 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-483090
DOI:	10.1038/emboj.2012.225
Journal or Publication Title:	Embo J.
Volume:	31
Number:	18
Page Range:	S. 3691 - 3704
Date:	2012
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1460-2075
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MONITORING AUTOPHAGY; ALPHA-MANNOSIDASE; SELECTIVE TRANSPORT; YEAST; COMPLEX; SYSTEM; LC3; CYTOPLASM; RECEPTOR; PHOSPHORYLATION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48309