8afq

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]}

References

1. ↑ 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
2. ↑ 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:http://dx.doi.org/10.1002/yea.764
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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:http://dx.doi.org/10.1091/mbc.E04-02-0147
7. ↑ 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:http://dx.doi.org/10.1074/jbc.M401066200
8. ↑ 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:http://dx.doi.org/10.1016/j.febslet.2006.07.041
9. ↑ 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:http://dx.doi.org/E07-04-0301
10. ↑ 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:http://dx.doi.org/10.1074/jbc.M803180200
11. ↑ 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:http://dx.doi.org/10.4161/auto.6801
12. ↑ 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:http://dx.doi.org/10.1038/emboj.2008.248
13. ↑ 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:http://dx.doi.org/10.1074/jbc.M109.080374
14. ↑ 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:http://dx.doi.org/10.4161/auto.7.12.18424
15. ↑ 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:http://dx.doi.org/10.1016/j.febslet.2012.06.008
16. ↑ 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:http://dx.doi.org/10.1091/mbc.E12-05-0347
17. ↑ 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:http://dx.doi.org/10.4161/auto.28971