Pex3 and Atg37 compete to regulate the interaction between the pexophagy receptor, Atg30, and the Hrr25 kinase.
| Title: | Pex3 and Atg37 compete to regulate the interaction between the pexophagy receptor, Atg30, and the Hrr25 kinase. |
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| Authors: | Zientara-Rytter K; a Section of Molecular Biology, Division of Biological Sciences , University California , San Diego , CA 92093-0322 , USA.; Ozeki K; a Section of Molecular Biology, Division of Biological Sciences , University California , San Diego , CA 92093-0322 , USA.; Nazarko TY; a Section of Molecular Biology, Division of Biological Sciences , University California , San Diego , CA 92093-0322 , USA.; Subramani S; a Section of Molecular Biology, Division of Biological Sciences , University California , San Diego , CA 92093-0322 , USA. |
| Source: | Autophagy [Autophagy] 2018; Vol. 14 (3), pp. 368-384. Date of Electronic Publication: 2018 Jan 29. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101265188 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8635 (Electronic) Linking ISSN: 15548627 NLM ISO Abbreviation: Autophagy Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : Philadelphia, PA : Taylor & Francis; Original Publication: Georgetown, TX : Landes Bioscience, 2005- |
| MeSH Terms: | Autophagy/*physiology ; Casein Kinase I/*metabolism ; Lipoproteins/*metabolism ; Membrane Proteins/*metabolism ; Peroxins/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism; Saccharomyces cerevisiae/metabolism ; Humans |
| Abstract: | Macroautophagy/autophagy is a highly conserved process in which subcellular components destined for degradation are sequestered within autophagosomes. The selectivity of autophagy is determined by autophagy receptors, such as Pichia pastoris Atg30 (autophagy-related 30), which controls the selective degradation of peroxisomes (pexophagy) through the assembly of a receptor-protein complex (RPC). Previously, we proved that the peroxisomal acyl-CoA-binding protein, Atg37, and the highly conserved peroxin, Pex3, are required for RPC formation and efficient pexophagy. Here, we describe how Atg37 and Pex3 regulate the assembly and activation of the pexophagic RPC. We demonstrate that Atg30 requires both Atg37 and Pex3 to recruit Atg8 and Atg11 to the pexophagic RPC, because Atg37 depends on Pex3 for its localization at the peroxisomal membrane. We establish that due to close proximity of Atg37- and Pex3-binding sites in the middle domain of Atg30, the binding of these proteins to Atg30 is mutually exclusive within this region. We also show that direct binding of Pex3 and Atg37 to Atg30 regulates its phosphorylation by the Hrr25 kinase, negatively and positively, respectively. Based on these results we present a model that clarifies the assembly and activation of the pexophagic RPC through the phosphoregulation of Atg30. |
| References: | J Biol Chem. 2000 Apr 7;275(14):9986-95. (PMID: 10744674); FEBS Lett. 2014 Nov 3;588(21):3862-9. (PMID: 25281559); Autophagy. 2015;11(2):432-3. (PMID: 25700828); Dev Cell. 2008 Mar;14(3):365-76. (PMID: 18331717); Autophagy. 2014 Jul;10(7):1348-9. (PMID: 24905344); Methods Enzymol. 2002;350:87-96. (PMID: 12073338); Mol Biol Cell. 2005 Apr;16(4):1593-605. (PMID: 15659643); Methods Mol Biol. 1998;103:27-39. (PMID: 9680631); Autophagy. 2012 Nov;8(11):1680-1. (PMID: 22874561); Nat Rev Mol Cell Biol. 2016 Sep;17 (9):537-52. (PMID: 27381245); Biochim Biophys Acta. 2009 Sep;1793(9):1404-12. (PMID: 19264099); EMBO J. 2012 Jun 29;31(13):2852-68. (PMID: 22643220); Biotechniques. 1997 Sep;23(3):409-12. (PMID: 9298207); Biochem Soc Trans. 2016 Apr 15;44(2):431-40. (PMID: 27068951); Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10315-20. (PMID: 8816797); J Cell Biol. 2014 Oct 13;207 (1):91-105. (PMID: 25287303); Mol Cell. 2015 Aug 6;59(3):372-81. (PMID: 26166702); EMBO Rep. 2014 Aug;15(8):862-70. (PMID: 24968893); Mol Cell. 2016 Oct 20;64(2):221-235. (PMID: 27768871); J Cell Biol. 2014 Feb 17;204(4):541-57. (PMID: 24535825); J Biol Chem. 2015 Mar 27;290(13):8623-31. (PMID: 25694426); EMBO Rep. 2013 May;14 (5):441-9. (PMID: 23559066); Nucleic Acids Res. 1988 Nov 25;16(22):10881-90. (PMID: 2849754); Cell Res. 2014 Jan;24(1):24-41. (PMID: 24366339) |
| Grant Information: | R01 DK041737 United States DK NIDDK NIH HHS; R35 GM119571 United States GM NIGMS NIH HHS; R37 DK041737 United States DK NIDDK NIH HHS; R56 DK041737 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: Atg30; Atg37; Pex3; autophagic receptor; peroxin; peroxisome; pexophagy; receptor-protein complex; selective autophagy |
| Substance Nomenclature: | 0 (Lipoproteins); 0 (Membrane Proteins); 0 (PEX3 protein, S cerevisiae); 0 (Peroxins); 0 (Pex3 protein, human); 0 (Saccharomyces cerevisiae Proteins); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (HRR25 protein, S cerevisiae) |
| Entry Date(s): | Date Created: 20171221 Date Completed: 20190322 Latest Revision: 20201214 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5915033 |
| DOI: | 10.1080/15548627.2017.1413521 |
| PMID: | 29260977 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't