Cargando…
Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins
Autophagy, a conserved membrane trafficking process, sequesters cytoplasmic components into autophagosomes and targets them for lysosomal degradation. The TNF receptor Fn14 participates in multiple intracellular signaling pathways and is strongly induced upon tissue injury and solid tumorigenesis. W...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138730/ https://www.ncbi.nlm.nih.gov/pubmed/30218067 http://dx.doi.org/10.1038/s41467-018-06275-1 |
_version_ | 1783355388038479872 |
---|---|
author | Winer, Hila Fraiberg, Milana Abada, Adi Dadosh, Tali Tamim-Yecheskel, Bat-Chen Elazar, Zvulun |
author_facet | Winer, Hila Fraiberg, Milana Abada, Adi Dadosh, Tali Tamim-Yecheskel, Bat-Chen Elazar, Zvulun |
author_sort | Winer, Hila |
collection | PubMed |
description | Autophagy, a conserved membrane trafficking process, sequesters cytoplasmic components into autophagosomes and targets them for lysosomal degradation. The TNF receptor Fn14 participates in multiple intracellular signaling pathways and is strongly induced upon tissue injury and solid tumorigenesis. While Fn14 is a short-lived protein, the regulation of its levels is largely obscure. Here we uncover a role for autophagy in Fn14 turnover, wherein specific core autophagy Atg8 proteins play distinct roles: Fn14 accumulates in the ERGIC in absence of GABARAP but within endosomes in the vicinity of autophagic membranes in absence of GATE-16. Moreover, GABARAP regulates overall cellular levels of Fn14, whereas GATE-16 regulates TWEAK signaling by Fn14 and thereby NF-κB activity. These findings not only implicate different Atg8 proteins in distinct roles within the mechanism of selective autophagic regulation of Fn14, but may also provide a more general view of their role in mediating autophagosome biogenesis from different membrane sources. |
format | Online Article Text |
id | pubmed-6138730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61387302018-09-17 Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins Winer, Hila Fraiberg, Milana Abada, Adi Dadosh, Tali Tamim-Yecheskel, Bat-Chen Elazar, Zvulun Nat Commun Article Autophagy, a conserved membrane trafficking process, sequesters cytoplasmic components into autophagosomes and targets them for lysosomal degradation. The TNF receptor Fn14 participates in multiple intracellular signaling pathways and is strongly induced upon tissue injury and solid tumorigenesis. While Fn14 is a short-lived protein, the regulation of its levels is largely obscure. Here we uncover a role for autophagy in Fn14 turnover, wherein specific core autophagy Atg8 proteins play distinct roles: Fn14 accumulates in the ERGIC in absence of GABARAP but within endosomes in the vicinity of autophagic membranes in absence of GATE-16. Moreover, GABARAP regulates overall cellular levels of Fn14, whereas GATE-16 regulates TWEAK signaling by Fn14 and thereby NF-κB activity. These findings not only implicate different Atg8 proteins in distinct roles within the mechanism of selective autophagic regulation of Fn14, but may also provide a more general view of their role in mediating autophagosome biogenesis from different membrane sources. Nature Publishing Group UK 2018-09-14 /pmc/articles/PMC6138730/ /pubmed/30218067 http://dx.doi.org/10.1038/s41467-018-06275-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Winer, Hila Fraiberg, Milana Abada, Adi Dadosh, Tali Tamim-Yecheskel, Bat-Chen Elazar, Zvulun Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins |
title | Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins |
title_full | Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins |
title_fullStr | Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins |
title_full_unstemmed | Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins |
title_short | Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8 proteins |
title_sort | autophagy differentially regulates tnf receptor fn14 by distinct mammalian atg8 proteins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138730/ https://www.ncbi.nlm.nih.gov/pubmed/30218067 http://dx.doi.org/10.1038/s41467-018-06275-1 |
work_keys_str_mv | AT winerhila autophagydifferentiallyregulatestnfreceptorfn14bydistinctmammalianatg8proteins AT fraibergmilana autophagydifferentiallyregulatestnfreceptorfn14bydistinctmammalianatg8proteins AT abadaadi autophagydifferentiallyregulatestnfreceptorfn14bydistinctmammalianatg8proteins AT dadoshtali autophagydifferentiallyregulatestnfreceptorfn14bydistinctmammalianatg8proteins AT tamimyecheskelbatchen autophagydifferentiallyregulatestnfreceptorfn14bydistinctmammalianatg8proteins AT elazarzvulun autophagydifferentiallyregulatestnfreceptorfn14bydistinctmammalianatg8proteins |