| Structural highlights
Function
ATG18_YEAST The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). May negatively regulate FAB1 activity by sequestering or masking VAC7 from FAB1. Necessary for proper vacuole morphology. Plays an important role in osmotically-induced vacuole fragmentation. Required for cytoplasm to vacuole transport (Cvt) vesicle formation, pexophagy and starvation-induced autophagy. Involved in correct ATG9 trafficking to the pre-autophagosomal structure. Might also be involved in premeiotic DNA replication. With ATG2, protects ATG8 from ATG4-mediated cleavage.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]
Publication Abstract from PubMed
Autophagy-related protein 18 (Atg18) participates in the elongation of early autophagosomal structures in concert with Atg2 and Atg9 complexes. How Atg18 contributes to the structural coordination of Atg2 and Atg9 at the isolation membrane remains to be understood. Here, we determined the cryo-EM structures of Atg18 organized in helical tubes, Atg18 oligomers in solution as well as on lipid membrane scaffolds. The helical assembly is composed of Atg18 tetramers forming a lozenge cylindrical lattice with remarkable structural similarity to the COPII outer coat. When reconstituted with lipid membranes, using subtomogram averaging we determined tilted Atg18 dimer structures bridging two juxtaposed lipid membranes spaced apart by 80 A. Moreover, lipid reconstitution experiments further delineate the contributions of Atg18's FRRG motif and the amphipathic helical extension in membrane interaction. The observed structural plasticity of Atg18's oligomeric organization and membrane binding properties provide a molecular framework for the positioning of downstream components of the autophagy machinery.
Atg18 oligomer organization in assembled tubes and on lipid membrane scaffolds.,Mann D, Fromm SA, Martinez-Sanchez A, Gopaldass N, Choy R, Mayer A, Sachse C Nat Commun. 2023 Dec 6;14(1):8086. doi: 10.1038/s41467-023-43460-3. PMID:38057304[18]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rabitsch KP, Toth A, Galova M, Schleiffer A, Schaffner G, Aigner E, Rupp C, Penkner AM, Moreno-Borchart AC, Primig M, Esposito RE, Klein F, Knop M, Nasmyth K. A screen for genes required for meiosis and spore formation based on whole-genome expression. Curr Biol. 2001 Jul 10;11(13):1001-9. PMID:11470404
- ↑ Georgakopoulos T, Koutroubas G, Vakonakis I, Tzermia M, Prokova V, Voutsina A, Alexandraki D. Functional analysis of the Saccharomyces cerevisiae YFR021w/YGR223c/YPL100w ORF family suggests relations to mitochondrial/peroxisomal functions and amino acid signalling pathways. Yeast. 2001 Sep 15;18(12):1155-71. PMID:11536337 doi:https://dx.doi.org/10.1002/yea.764
- ↑ Barth H, Meiling-Wesse K, Epple UD, Thumm M. Autophagy and the cytoplasm to vacuole targeting pathway both require Aut10p. FEBS Lett. 2001 Nov 9;508(1):23-8. PMID:11707261
- ↑ Guan J, Stromhaug PE, George MD, Habibzadegah-Tari P, Bevan A, Dunn WA Jr, Klionsky DJ. Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris. Mol Biol Cell. 2001 Dec;12(12):3821-38. PMID:11739783
- ↑ Reggiori F, Tucker KA, Stromhaug PE, Klionsky DJ. The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev Cell. 2004 Jan;6(1):79-90. PMID:14723849
- ↑ Stromhaug PE, Reggiori F, Guan J, Wang CW, Klionsky DJ. Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol Biol Cell. 2004 Aug;15(8):3553-66. Epub 2004 May 21. PMID:15155809 doi:https://dx.doi.org/10.1091/mbc.E04-02-0147
- ↑ Meiling-Wesse K, Barth H, Voss C, Eskelinen EL, Epple UD, Thumm M. Atg21 is required for effective recruitment of Atg8 to the preautophagosomal structure during the Cvt pathway. J Biol Chem. 2004 Sep 3;279(36):37741-50. doi: 10.1074/jbc.M401066200. Epub 2004 , Jun 11. PMID:15194695 doi:https://dx.doi.org/10.1074/jbc.M401066200
- ↑ Krick R, Tolstrup J, Appelles A, Henke S, Thumm M. The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy. FEBS Lett. 2006 Aug 21;580(19):4632-8. doi: 10.1016/j.febslet.2006.07.041. Epub, 2006 Jul 21. PMID:16876790 doi:https://dx.doi.org/10.1016/j.febslet.2006.07.041
- ↑ Efe JA, Botelho RJ, Emr SD. Atg18 regulates organelle morphology and Fab1 kinase activity independent of its membrane recruitment by phosphatidylinositol 3,5-bisphosphate. Mol Biol Cell. 2007 Nov;18(11):4232-44. Epub 2007 Aug 15. PMID:17699591 doi:https://dx.doi.org/E07-04-0301
- ↑ Obara K, Sekito T, Niimi K, Ohsumi Y. The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J Biol Chem. 2008 Aug 29;283(35):23972-80. doi: 10.1074/jbc.M803180200. Epub 2008, Jun 27. PMID:18586673 doi:https://dx.doi.org/10.1074/jbc.M803180200
- ↑ Krick R, Henke S, Tolstrup J, Thumm M. Dissecting the localization and function of Atg18, Atg21 and Ygr223c. Autophagy. 2008 Oct;4(7):896-910. doi: 10.4161/auto.6801. Epub 2008 Oct 18. PMID:18769150 doi:https://dx.doi.org/10.4161/auto.6801
- ↑ Jin N, Chow CY, Liu L, Zolov SN, Bronson R, Davisson M, Petersen JL, Zhang Y, Park S, Duex JE, Goldowitz D, Meisler MH, Weisman LS. VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse. EMBO J. 2008 Dec 17;27(24):3221-34. doi: 10.1038/emboj.2008.248. Epub 2008 Nov, 27. PMID:19037259 doi:https://dx.doi.org/10.1038/emboj.2008.248
- ↑ Nair U, Cao Y, Xie Z, Klionsky DJ. Roles of the lipid-binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole targeting pathway and autophagy. J Biol Chem. 2010 Apr 9;285(15):11476-88. doi: 10.1074/jbc.M109.080374. Epub 2010, Feb 12. PMID:20154084 doi:https://dx.doi.org/10.1074/jbc.M109.080374
- ↑ Nair U, Thumm M, Klionsky DJ, Krick R. GFP-Atg8 protease protection as a tool to monitor autophagosome biogenesis. Autophagy. 2011 Dec;7(12):1546-50. doi: 10.4161/auto.7.12.18424. PMID:22108003 doi:https://dx.doi.org/10.4161/auto.7.12.18424
- ↑ Kobayashi T, Suzuki K, Ohsumi Y. Autophagosome formation can be achieved in the absence of Atg18 by expressing engineered PAS-targeted Atg2. FEBS Lett. 2012 Jul 30;586(16):2473-8. doi: 10.1016/j.febslet.2012.06.008. Epub, 2012 Jun 19. PMID:22728243 doi:https://dx.doi.org/10.1016/j.febslet.2012.06.008
- ↑ Zieger M, Mayer A. Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements. Mol Biol Cell. 2012 Sep;23(17):3438-49. doi: 10.1091/mbc.E12-05-0347. Epub 2012, Jul 11. PMID:22787281 doi:https://dx.doi.org/10.1091/mbc.E12-05-0347
- ↑ Papinski D, Kraft C. Atg1 kinase organizes autophagosome formation by phosphorylating Atg9. Autophagy. 2014 Jul;10(7):1338-40. doi: 10.4161/auto.28971. Epub 2014 Apr 28. PMID:24905091 doi:https://dx.doi.org/10.4161/auto.28971
- ↑ Mann D, Fromm SA, Martinez-Sanchez A, Gopaldass N, Choy R, Mayer A, Sachse C. Atg18 oligomer organization in assembled tubes and on lipid membrane scaffolds. Nat Commun. 2023 Dec 6;14(1):8086. PMID:38057304 doi:10.1038/s41467-023-43460-3
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