Cargando…
The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila
The large-scale turnover of intracellular material including organelles is achieved by autophagy-mediated degradation in lysosomes. Initiation of autophagy is controlled by a protein kinase complex consisting of an Atg1-family kinase, Atg13, FIP200/Atg17, and the metazoan-specific subunit Atg101. He...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034400/ https://www.ncbi.nlm.nih.gov/pubmed/24895579 http://dx.doi.org/10.1155/2014/470482 |
_version_ | 1782317958729564160 |
---|---|
author | Hegedűs, Krisztina Nagy, Péter Gáspári, Zoltán Juhász, Gábor |
author_facet | Hegedűs, Krisztina Nagy, Péter Gáspári, Zoltán Juhász, Gábor |
author_sort | Hegedűs, Krisztina |
collection | PubMed |
description | The large-scale turnover of intracellular material including organelles is achieved by autophagy-mediated degradation in lysosomes. Initiation of autophagy is controlled by a protein kinase complex consisting of an Atg1-family kinase, Atg13, FIP200/Atg17, and the metazoan-specific subunit Atg101. Here we show that loss of Atg101 impairs both starvation-induced and basal autophagy in Drosophila. This leads to accumulation of protein aggregates containing the selective autophagy cargo ref(2)P/p62. Mapping experiments suggest that Atg101 binds to the N-terminal HORMA domain of Atg13 and may also interact with two unstructured regions of Atg1. Another HORMA domain-containing protein, Mad2, forms a conformational homodimer. We show that Drosophila Atg101 also dimerizes, and it is predicted to fold into a HORMA domain. Atg101 interacts with ref(2)P as well, similar to Atg13, Atg8a, Atg16, Atg18, Keap1, and RagC, a known regulator of Tor kinase which coordinates cell growth and autophagy. These results raise the possibility that the interactions and dimerization of the putative HORMA domain protein Atg101 play critical roles in starvation-induced autophagy and proteostasis, by promoting the formation of protein aggregate-containing autophagosomes. |
format | Online Article Text |
id | pubmed-4034400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40344002014-06-03 The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila Hegedűs, Krisztina Nagy, Péter Gáspári, Zoltán Juhász, Gábor Biomed Res Int Research Article The large-scale turnover of intracellular material including organelles is achieved by autophagy-mediated degradation in lysosomes. Initiation of autophagy is controlled by a protein kinase complex consisting of an Atg1-family kinase, Atg13, FIP200/Atg17, and the metazoan-specific subunit Atg101. Here we show that loss of Atg101 impairs both starvation-induced and basal autophagy in Drosophila. This leads to accumulation of protein aggregates containing the selective autophagy cargo ref(2)P/p62. Mapping experiments suggest that Atg101 binds to the N-terminal HORMA domain of Atg13 and may also interact with two unstructured regions of Atg1. Another HORMA domain-containing protein, Mad2, forms a conformational homodimer. We show that Drosophila Atg101 also dimerizes, and it is predicted to fold into a HORMA domain. Atg101 interacts with ref(2)P as well, similar to Atg13, Atg8a, Atg16, Atg18, Keap1, and RagC, a known regulator of Tor kinase which coordinates cell growth and autophagy. These results raise the possibility that the interactions and dimerization of the putative HORMA domain protein Atg101 play critical roles in starvation-induced autophagy and proteostasis, by promoting the formation of protein aggregate-containing autophagosomes. Hindawi Publishing Corporation 2014 2014-05-08 /pmc/articles/PMC4034400/ /pubmed/24895579 http://dx.doi.org/10.1155/2014/470482 Text en Copyright © 2014 Krisztina Hegedűs et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hegedűs, Krisztina Nagy, Péter Gáspári, Zoltán Juhász, Gábor The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila |
title | The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila
|
title_full | The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila
|
title_fullStr | The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila
|
title_full_unstemmed | The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila
|
title_short | The Putative HORMA Domain Protein Atg101 Dimerizes and Is Required for Starvation-Induced and Selective Autophagy in Drosophila
|
title_sort | putative horma domain protein atg101 dimerizes and is required for starvation-induced and selective autophagy in drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034400/ https://www.ncbi.nlm.nih.gov/pubmed/24895579 http://dx.doi.org/10.1155/2014/470482 |
work_keys_str_mv | AT hegeduskrisztina theputativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT nagypeter theputativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT gasparizoltan theputativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT juhaszgabor theputativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT hegeduskrisztina putativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT nagypeter putativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT gasparizoltan putativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila AT juhaszgabor putativehormadomainproteinatg101dimerizesandisrequiredforstarvationinducedandselectiveautophagyindrosophila |