Regulation of LC3 lipidation by the autophagy-specific class III phosphatidylinositol-3 kinase complex

Brier, Livia W.; Ge, Liang; Stjepanovic, Goran; Thelen, Ashley M.; Hurley, James H.; Schekman, Randy

doi:10.1091/mbc.e18-11-0743

Regulation of LC3 lipidation by the autophagy-specific class III phosphatidylinositol-3 kinase complex

Journal Article · Mon Apr 15 00:00:00 EDT 2019 · Molecular Biology of the Cell

DOI:https://doi.org/10.1091/mbc.e18-11-0743· OSTI ID:1625250

Brier, Livia W. ^[1]; Ge, Liang ^[2]; Stjepanovic, Goran ^[3]; Thelen, Ashley M. ^[4]; Hurley, James H. ^[3]; Schekman, Randy ^[2]

Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; DOE/OSTI
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology

Autophagy is a conserved eukaryotic pathway critical for cellular adaptation to changes in nutrition levels and stress. The class III phosphatidylinositol (PI)3-kinase complexes I and II (PI3KC3-C1 and -C2) are essential for autophagosome initiation and maturation, respectively, from highly curved vesicles. We used a cell-free reaction that reproduces a key autophagy initiation step, LC3 lipidation, as a biochemical readout to probe the role of autophagy-related gene (ATG)14, a PI3KC3-C1-specific subunit implicated in targeting the complex to autophagy initiation sites. We reconstituted LC3 lipidation with recombinant PI3KC3-C1, -C2, or various mutant derivatives added to extracts derived from a CRISPR/Cas9-generated ATG14-knockout cell line. Both complexes C1 and C2 require the C-terminal helix of VPS34 for activity on highly curved membranes. However, only complex C1 supports LC3 lipidation through the curvature-targeting amphipathic lipid packing sensor (ALPS) motif of ATG14. Furthermore, the ALPS motif and VPS34 catalytic activity are required for downstream recruitment of WD-repeat domain phosphoinositide-interacting protein (WIPI)2, a protein that binds phosphatidylinositol 3-phosphate and its product phosphatidylinositol 3, 5-bisphosphate, and a WIPI-binding protein, ATG2A, but do not affect membrane association of ATG3 and ATG16L1, enzymes contributing directly to LC3 lipidation. These data reveal the nuanced role of the ATG14 ALPS in membrane curvature sensing, suggesting that the ALPS has additional roles in supporting LC3 lipidation.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625250

Journal Information:: Molecular Biology of the Cell, Journal Name: Molecular Biology of the Cell Journal Issue: 9 Vol. 30; ISSN 1059-1524

Publisher:: American Society for Cell BiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (72)

The protein-vesicle network of autophagy Ge, Liang; Baskaran, Sulochanadevi; Schekman, Randy Current Opinion in Cell Biology, Vol. 29 https://doi.org/10.1016/j.ceb.2014.02.005	journal	August 2014
Mechanisms of Autophagosome Biogenesis Rubinsztein, David C.; Shpilka, Tomer; Elazar, Zvulun Current Biology, Vol. 22, Issue 1 https://doi.org/10.1016/j.cub.2011.11.034	journal	January 2012
Sensing Membrane Curvature in Macroautophagy Nguyen, Nathan; Shteyn, Vladimir; Melia, Thomas J. Journal of Molecular Biology, Vol. 429, Issue 4 https://doi.org/10.1016/j.jmb.2017.01.006	journal	February 2017
WIPI2 Links LC3 Conjugation with PI3P, Autophagosome Formation, and Pathogen Clearance by Recruiting Atg12–5-16L1 Dooley, Hannah C.; Razi, Minoo; Polson, Hannah E. J. Molecular Cell, Vol. 55, Issue 2 https://doi.org/10.1016/j.molcel.2014.05.021	journal	July 2014
Discovery of (2 S )-8-[(3 R )-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2 H -pyrimido[1,2- a ]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors Pasquier, Benoit; El-Ahmad, Youssef; Filoche-Rommé, Bruno Journal of Medicinal Chemistry, Vol. 58, Issue 1 https://doi.org/10.1021/jm5013352	journal	July 2014
FIP200 regulates targeting of Atg16L1 to the isolation membrane Nishimura, Taki; Kaizuka, Takeshi; Cadwell, Ken EMBO reports, Vol. 14, Issue 3 https://doi.org/10.1038/embor.2013.6	journal	February 2013
Network organization of the human autophagy system Behrends, Christian; Sowa, Mathew E.; Gygi, Steven P. Nature, Vol. 466, Issue 7302 https://doi.org/10.1038/nature09204	journal	June 2010
UVRAG reveals its second nature Peplowska, Karolina; Cabrera, Margarita; Ungermann, Christian Nature Cell Biology, Vol. 10, Issue 7 https://doi.org/10.1038/ncb0708-759	journal	July 2008
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis Takahashi, Yoshinori; Coppola, Domenico; Matsushita, Norimasa Nature Cell Biology, Vol. 9, Issue 10 https://doi.org/10.1038/ncb1634	journal	September 2007
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages Matsunaga, Kohichi; Saitoh, Tatsuya; Tabata, Keisuke Nature Cell Biology, Vol. 11, Issue 4 https://doi.org/10.1038/ncb1846	journal	March 2009
Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex Zhong, Yun; Wang, Qing Jun; Li, Xianting Nature Cell Biology, Vol. 11, Issue 4 https://doi.org/10.1038/ncb1854	journal	March 2009
PtdIns(3)P-bound UVRAG coordinates Golgi–ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex He, Shanshan; Ni, Duojiao; Ma, Binyun Nature Cell Biology, Vol. 15, Issue 10 https://doi.org/10.1038/ncb2848	journal	September 2013
Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3 Nath, Sangeeta; Dancourt, Julia; Shteyn, Vladimir Nature Cell Biology, Vol. 16, Issue 5 https://doi.org/10.1038/ncb2940	journal	April 2014
WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy Bakula, Daniela; Müller, Amelie J.; Zuleger, Theresia Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15637	journal	May 2017
The autophagosome: origins unknown, biogenesis complex Lamb, Christopher A.; Yoshimori, Tamotsu; Tooze, Sharon A. Nature Reviews Molecular Cell Biology, Vol. 14, Issue 12 https://doi.org/10.1038/nrm3696	journal	November 2013
Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex–dependent and –independent autophagy Gammoh, Noor; Florey, Oliver; Overholtzer, Michael Nature Structural & Molecular Biology, Vol. 20, Issue 2 https://doi.org/10.1038/nsmb.2475	journal	December 2012
WIPI-1α (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy Proikas-Cezanne, Tassula; Waddell, Scott; Gaugel, Anja Oncogene, Vol. 23, Issue 58 https://doi.org/10.1038/sj.onc.1208331	journal	December 2004
Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase Sun, Q.; Fan, W.; Chen, K. Proceedings of the National Academy of Sciences, Vol. 105, Issue 49 https://doi.org/10.1073/pnas.0810452105	journal	December 2008
Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake Ge, L.; Qi, W.; Wang, L. -J. Proceedings of the National Academy of Sciences, Vol. 108, Issue 2 https://doi.org/10.1073/pnas.1014434108	journal	December 2010
Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy Young, Lindsey N.; Cho, Kelvin; Lawrence, Rosalie Proceedings of the National Academy of Sciences, Vol. 113, Issue 29 https://doi.org/10.1073/pnas.1603650113	journal	July 2016
Nrbf2 Protein Suppresses Autophagy by Modulating Atg14L Protein-containing Beclin 1-Vps34 Complex Architecture and Reducing Intracellular Phosphatidylinositol-3 Phosphate Levels Zhong, Yu; Morris, Deanna H.; Jin, Lin Journal of Biological Chemistry, Vol. 289, Issue 38 https://doi.org/10.1074/jbc.m114.561134	journal	August 2014
MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy Ma, Xi; Zhang, Shen; He, Long Autophagy, Vol. 13, Issue 3 https://doi.org/10.1080/15548627.2016.1269988	journal	January 2017
Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells Mizushima, Noboru; Yamamoto, Akitsugu; Hatano, Masahiko Journal of Cell Biology, Vol. 152, Issue 4 https://doi.org/10.1083/jcb.152.4.657	journal	February 2001
Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum Axe, Elizabeth L.; Walker, Simon A.; Manifava, Maria Journal of Cell Biology, Vol. 182, Issue 4 https://doi.org/10.1083/jcb.200803137	journal	August 2008
Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG Itakura, Eisuke; Kishi, Chieko; Inoue, Kinji Molecular Biology of the Cell, Vol. 19, Issue 12 https://doi.org/10.1091/mbc.e08-01-0080	journal	December 2008
Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets Velikkakath, Anoop Kumar G.; Nishimura, Taki; Oita, Eiko Molecular Biology of the Cell, Vol. 23, Issue 5 https://doi.org/10.1091/mbc.e11-09-0785	journal	March 2012
ER exit sites are physical and functional core autophagosome biogenesis components Graef, Martin; Friedman, Jonathan R.; Graham, Christopher Molecular Biology of the Cell, Vol. 24, Issue 18 https://doi.org/10.1091/mbc.e13-07-0381	journal	September 2013
HELIQUEST: a web server to screen sequences with specific -helical properties Gautier, R.; Douguet, D.; Antonny, B. Bioinformatics, Vol. 24, Issue 18 https://doi.org/10.1093/bioinformatics/btn392	journal	July 2008
Hierarchy of Atg proteins in pre-autophagosomal structure organization Suzuki, Kuninori; Kubota, Yuka; Sekito, Takayuki Genes to Cells, Vol. 12, Issue 2 https://doi.org/10.1111/j.1365-2443.2007.01050.x	journal	February 2007
Transport of phosphatidylinositol 3-phosphate into the vacuole via autophagic membranes in Saccharomyces cerevisiae Obara, Keisuke; Noda, Takeshi; Niimi, Kaori Genes to Cells, Vol. 13, Issue 6 https://doi.org/10.1111/j.1365-2443.2008.01188.x	journal	June 2008
The Phosphatidylinositol 3-Kinase Inhibitors Wortmannin and LY294002 Inhibit Autophagy in Isolated Rat Hepatocytes Blommaart, Edward F. C.; Krause, Ulrike; Schellens, Jacques P. M. European Journal of Biochemistry, Vol. 243, Issue 1-2 https://doi.org/10.1111/j.1432-1033.1997.0240a.x	journal	January 1997
Shaping Development of Autophagy Inhibitors with the Structure of the Lipid Kinase Vps34 Miller, S.; Tavshanjian, B.; Oleksy, A. Science, Vol. 327, Issue 5973 https://doi.org/10.1126/science.1184429	journal	March 2010
Multiplex Genome Engineering Using CRISPR/Cas Systems Cong, L.; Ran, F. A.; Cox, D. Science, Vol. 339, Issue 6121, p. 819-823 https://doi.org/10.1126/science.1231143	journal	January 2013
Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes Rostislavleva, K.; Soler, N.; Ohashi, Y. Science, Vol. 350, Issue 6257 https://doi.org/10.1126/science.aac7365	journal	October 2015
Mechanisms of Membrane Curvature Sensing Antonny, Bruno Annual Review of Biochemistry, Vol. 80, Issue 1 https://doi.org/10.1146/annurev-biochem-052809-155121	journal	July 2011
Fine mapping of autophagy-related proteins during autophagosome formation in Saccharomyces cerevisiae Suzuki, K.; Akioka, M.; Kondo-Kakuta, C. Journal of Cell Science, Vol. 126, Issue 11 https://doi.org/10.1242/jcs.122960	journal	April 2013
Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells Kishi-Itakura, C.; Koyama-Honda, I.; Itakura, E. Journal of Cell Science, Vol. 127, Issue 18 https://doi.org/10.1242/jcs.156034	journal	July 2014
A molecular perspective of mammalian autophagosome biogenesis Mercer, Thomas J.; Gubas, Andrea; Tooze, Sharon A. The Francis Crick Institute https://doi.org/10.25418/crick.15178986	text	January 2021
Temporal analysis of recruitment of mammalian ATG proteins to the autophagosome formation site Koyama-Honda, Ikuko; Itakura, Eisuke; Fujiwara, Takahiro K. Autophagy, Vol. 9, Issue 10 https://doi.org/10.4161/auto.25529	journal	October 2013
Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins Itakura, Eisuke; Mizushima, Noboru Autophagy, Vol. 6, Issue 6 https://doi.org/10.4161/auto.6.6.12709	journal	August 2010
Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy Takahashi, Yoshinori; Meyerkord, Cheryl L.; Hori, Tsukasa Autophagy, Vol. 7, Issue 1 https://doi.org/10.4161/auto.7.1.14015	journal	January 2011
Membrane curvature response in autophagy Wilz, Livia; Fan, Weiliang; Zhong, Qing Autophagy, Vol. 7, Issue 10 https://doi.org/10.4161/auto.7.10.16738	journal	October 2011
The ER–Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis Ge, Liang; Melville, David; Zhang, Min eLife, Vol. 2 https://doi.org/10.7554/elife.00947	journal	August 2013
Phosphatidylinositol 3-kinase and COPII generate LC3 lipidation vesicles from the ER-Golgi intermediate compartment Ge, Liang; Zhang, Min; Schekman, Randy eLife, Vol. 3 https://doi.org/10.7554/elife.04135	journal	November 2014
Differential Regulation of Distinct Vps34 Complexes by AMPK in Nutrient Stress and Autophagy Kim, Joungmok; Kim, Young Chul; Fang, Chong Cell, Vol. 152, Issue 1-2 https://doi.org/10.1016/j.cell.2012.12.016	journal	January 2013
Atomistic Autophagy: The Structures of Cellular Self-Digestion Hurley, James H.; Schulman, Brenda A. Cell, Vol. 157, Issue 2 https://doi.org/10.1016/j.cell.2014.01.070	journal	April 2014
mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation Kim, Young-Mi; Jung, Chang Hwa; Seo, Minchul Molecular Cell, Vol. 57, Issue 2 https://doi.org/10.1016/j.molcel.2014.11.013	journal	January 2015
Autophagy fights disease through cellular self-digestion Mizushima, Noboru; Levine, Beth; Cuervo, Ana Maria Nature, Vol. 451, Issue 7182 https://doi.org/10.1038/nature06639	journal	February 2008
Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking Liang, Chengyu; Lee, Jong-soo; Inn, Kyung-Soo Nature Cell Biology, Vol. 10, Issue 7 https://doi.org/10.1038/ncb1740	journal	June 2008
A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy Ronan, Baptiste; Flamand, Odile; Vescovi, Lionel Nature Chemical Biology, Vol. 10, Issue 12 https://doi.org/10.1038/nchembio.1681	journal	October 2014
A general amphipathic α-helical motif for sensing membrane curvature Drin, Guillaume; Casella, Jean-François; Gautier, Romain Nature Structural & Molecular Biology, Vol. 14, Issue 2 https://doi.org/10.1038/nsmb1194	journal	January 2007
Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome Fox, Daniel; Mathur, Anukriti; Xue, Yansong Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-14534-3	journal	February 2020
Autophagy in Human Health and Disease Choi, Augustine M. K.; Ryter, Stefan W.; Levine, Beth New England Journal of Medicine, Vol. 368, Issue 7 https://doi.org/10.1056/NEJMra1205406	journal	February 2013
Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L) Fan, W.; Nassiri, A.; Zhong, Q. Proceedings of the National Academy of Sciences, Vol. 108, Issue 19 https://doi.org/10.1073/pnas.1016472108	journal	April 2011
Nrbf2 Protein Suppresses Autophagy by Modulating Atg14L Protein-containing Beclin 1-Vps34 Complex Architecture and Reducing Intracellular Phosphatidylinositol-3 Phosphate Levels Zhong, Yu; Morris, Deanna H.; Jin, Lin Journal of Biological Chemistry, Vol. 289, Issue 38 https://doi.org/10.1074/jbc.M114.561134	journal	August 2014
A molecular perspective of mammalian autophagosome biogenesis Mercer, Thomas J.; Gubas, Andrea; Tooze, Sharon A. Journal of Biological Chemistry, Vol. 293, Issue 15 https://doi.org/10.1074/jbc.R117.810366	journal	January 2018
Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L Matsunaga, Kohichi; Morita, Eiji; Saitoh, Tatsuya Journal of Cell Biology, Vol. 190, Issue 4 https://doi.org/10.1083/jcb.200911141	journal	August 2010
Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L Matsunaga, Kohichi; Morita, Eiji; Saitoh, Tatsuya The Journal of Experimental Medicine, Vol. 207, Issue 9 https://doi.org/10.1084/jem2079oia24	journal	August 2010
The Atg16L Complex Specifies the Site of LC3 Lipidation for Membrane Biogenesis in Autophagy Fujita, Naonobu; Itoh, Takashi; Omori, Hiroko Molecular Biology of the Cell, Vol. 19, Issue 5 https://doi.org/10.1091/mbc.e07-12-1257	journal	May 2008
FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct functions in the endosomal and Golgi compartments Ridley, S. H.; Ktistakis, N.; Davidson, K. Journal of Cell Science, Vol. 114, Issue 22 https://doi.org/10.1242/jcs.114.22.3991	journal	November 2001
Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells Kishi-Itakura, Chieko; Koyama-Honda, Ikuko; Itakura, Eisuke Journal of Cell Science, Vol. 127, Issue 22 https://doi.org/10.1242/jcs.164293	journal	November 2014
A molecular perspective of mammalian autophagosome biogenesis Mercer, Thomas J.; Gubas, Andrea; Tooze, Sharon A. The Francis Crick Institute https://doi.org/10.25418/crick.15178986.v1	text	January 2021
Atg14 and UVRAG: Mutually exclusive subunits of mammalian Beclin 1-PI3K complexes Itakura, Eisuke; Mizushima, Noboru Autophagy, Vol. 5, Issue 4 https://doi.org/10.4161/auto.5.4.8062	journal	May 2009
Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation Polson, Hannah E. J.; de Lartigue, Jane; Rigden, Daniel J. Autophagy, Vol. 6, Issue 4 https://doi.org/10.4161/auto.6.4.11863	journal	May 2010
What is the advantage of a transient precursor in autophagosome biogenesis? Ktistakis, Nicholas T.; Andrews, Simon; Long, Joshua Autophagy, Vol. 7, Issue 1 https://doi.org/10.4161/auto.7.1.13697	journal	January 2011
Resveratrol-mediated autophagy requires WIPI-1-regulated LC3 lipidation in the absence of induced phagophore formation Mauthe, Mario; Jacob, Anke; Freiberger, Sandra Autophagy, Vol. 7, Issue 12 https://doi.org/10.4161/auto.7.12.17802	journal	December 2011
RNA-programmed genome editing in human cells Jinek, Martin; East, Alexandra; Cheng, Aaron eLife Sciences Publications Ltd. https://doi.org/10.5167/uzh-79770	text	January 2013
RNA-programmed genome editing in human cells Jinek, Martin; East, Alexandra; Cheng, Aaron eLife, Vol. 2, Article No. e00471 https://doi.org/10.7554/eLife.00471	journal	January 2013
The ER–Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis Ge, Liang; Melville, David; Zhang, Min eLife, Vol. 2 https://doi.org/10.7554/eLife.00947	journal	August 2013
Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex Baskaran, Sulochanadevi; Carlson, Lars-Anders; Stjepanovic, Goran eLife, Vol. 3 https://doi.org/10.7554/eLife.05115	journal	December 2014
Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion Zhang, Min; Kenny, Samuel J.; Ge, Liang eLife, Vol. 4 https://doi.org/10.7554/eLife.11205	journal	November 2015
WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Bakula, Daniela; Müller, Amelie J.; Zuleger, Theresia Nature Publishing Group https://doi.org/10.7892/boris.105300	text	January 2017

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