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Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells

Although autophagic pathways are essential to developmental processes, many questions still remain regarding the initiation signals that regulate autophagy in the context of differentiation. To address these questions we studied the ocular lens, as the programmed elimination of nuclei and organelles...

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Autores principales: Basu, Subhasree, Rajakaruna, Suren, Reyes, Beverly, Van Bockstaele, Elisabeth, Menko, A Sue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203547/
https://www.ncbi.nlm.nih.gov/pubmed/24813396
http://dx.doi.org/10.4161/auto.28768
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author Basu, Subhasree
Rajakaruna, Suren
Reyes, Beverly
Van Bockstaele, Elisabeth
Menko, A Sue
author_facet Basu, Subhasree
Rajakaruna, Suren
Reyes, Beverly
Van Bockstaele, Elisabeth
Menko, A Sue
author_sort Basu, Subhasree
collection PubMed
description Although autophagic pathways are essential to developmental processes, many questions still remain regarding the initiation signals that regulate autophagy in the context of differentiation. To address these questions we studied the ocular lens, as the programmed elimination of nuclei and organelles occurs in a precisely regulated spatiotemporal manner to form the organelle-free zone (OFZ), a characteristic essential for vision acuity. Here, we report our discovery that inactivation of MAPK/JNK induces autophagy for formation of the OFZ through its regulation of MTORC1, where MAPK/JNK signaling is required for both MTOR activation and RPTOR/RAPTOR phosphorylation. Autophagy pathway proteins including ULK1, BECN1/Beclin 1, and MAP1LC3B2/LC3B-II were upregulated in the presence of inhibitors to either MAPK/JNK or MTOR, inducing autophagic loss of organelles to form the OFZ. These results reveal that MAPK/JNK is a positive regulator of MTORC1 signaling and its developmentally regulated inactivation provides an inducing signal for the coordinated autophagic removal of nuclei and organelles required for lens function.
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spelling pubmed-42035472015-07-01 Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells Basu, Subhasree Rajakaruna, Suren Reyes, Beverly Van Bockstaele, Elisabeth Menko, A Sue Autophagy Basic Research Paper Although autophagic pathways are essential to developmental processes, many questions still remain regarding the initiation signals that regulate autophagy in the context of differentiation. To address these questions we studied the ocular lens, as the programmed elimination of nuclei and organelles occurs in a precisely regulated spatiotemporal manner to form the organelle-free zone (OFZ), a characteristic essential for vision acuity. Here, we report our discovery that inactivation of MAPK/JNK induces autophagy for formation of the OFZ through its regulation of MTORC1, where MAPK/JNK signaling is required for both MTOR activation and RPTOR/RAPTOR phosphorylation. Autophagy pathway proteins including ULK1, BECN1/Beclin 1, and MAP1LC3B2/LC3B-II were upregulated in the presence of inhibitors to either MAPK/JNK or MTOR, inducing autophagic loss of organelles to form the OFZ. These results reveal that MAPK/JNK is a positive regulator of MTORC1 signaling and its developmentally regulated inactivation provides an inducing signal for the coordinated autophagic removal of nuclei and organelles required for lens function. Landes Bioscience 2014-07-01 2014-05-09 /pmc/articles/PMC4203547/ /pubmed/24813396 http://dx.doi.org/10.4161/auto.28768 Text en Copyright © 2014 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Basic Research Paper
Basu, Subhasree
Rajakaruna, Suren
Reyes, Beverly
Van Bockstaele, Elisabeth
Menko, A Sue
Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
title Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
title_full Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
title_fullStr Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
title_full_unstemmed Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
title_short Suppression of MAPK/JNK-MTORC1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
title_sort suppression of mapk/jnk-mtorc1 signaling leads to premature loss of organelles and nuclei by autophagy during terminal differentiation of lens fiber cells
topic Basic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203547/
https://www.ncbi.nlm.nih.gov/pubmed/24813396
http://dx.doi.org/10.4161/auto.28768
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