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GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration
Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophag...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294778/ https://www.ncbi.nlm.nih.gov/pubmed/28053206 http://dx.doi.org/10.1083/jcb.201606020 |
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author | Wakatsuki, Shuji Tokunaga, Shinji Shibata, Megumi Araki, Toshiyuki |
author_facet | Wakatsuki, Shuji Tokunaga, Shinji Shibata, Megumi Araki, Toshiyuki |
author_sort | Wakatsuki, Shuji |
collection | PubMed |
description | Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)–mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration. Phosphorylated MCL1 is ubiquitinated by the FBXW7 ubiquitin ligase and degraded by the proteasome, thereby releasing BECLIN1 to induce axonal autophagy. Axonal autophagy contributes to local adenosine triphosphate production in degenerating axons and the exposure of phosphatidylserine—an “eat-me” signal for phagocytes—on transected axons and is required for normal recruitment of phagocytes to axonal debris in vivo. These results suggest that GSK3B–MCL1 signaling to regulate autophagy might be important for the successful completion of Wallerian degeneration. |
format | Online Article Text |
id | pubmed-5294778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52947782017-08-01 GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration Wakatsuki, Shuji Tokunaga, Shinji Shibata, Megumi Araki, Toshiyuki J Cell Biol Research Articles Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)–mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration. Phosphorylated MCL1 is ubiquitinated by the FBXW7 ubiquitin ligase and degraded by the proteasome, thereby releasing BECLIN1 to induce axonal autophagy. Axonal autophagy contributes to local adenosine triphosphate production in degenerating axons and the exposure of phosphatidylserine—an “eat-me” signal for phagocytes—on transected axons and is required for normal recruitment of phagocytes to axonal debris in vivo. These results suggest that GSK3B–MCL1 signaling to regulate autophagy might be important for the successful completion of Wallerian degeneration. The Rockefeller University Press 2017-02 /pmc/articles/PMC5294778/ /pubmed/28053206 http://dx.doi.org/10.1083/jcb.201606020 Text en © 2017 Wakatsuki et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Wakatsuki, Shuji Tokunaga, Shinji Shibata, Megumi Araki, Toshiyuki GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration |
title | GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration |
title_full | GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration |
title_fullStr | GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration |
title_full_unstemmed | GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration |
title_short | GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration |
title_sort | gsk3b-mediated phosphorylation of mcl1 regulates axonal autophagy to promote wallerian degeneration |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294778/ https://www.ncbi.nlm.nih.gov/pubmed/28053206 http://dx.doi.org/10.1083/jcb.201606020 |
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