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Drosophila to Explore Nucleolar Stress
Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. Drosophila offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy dependin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267670/ https://www.ncbi.nlm.nih.gov/pubmed/34201772 http://dx.doi.org/10.3390/ijms22136759 |
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author | DeLeo, Kathryn R. Baral, Sonu S. Houser, Alex James, Allison Sewell, Phelan Pandey, Shova DiMario, Patrick J. |
author_facet | DeLeo, Kathryn R. Baral, Sonu S. Houser, Alex James, Allison Sewell, Phelan Pandey, Shova DiMario, Patrick J. |
author_sort | DeLeo, Kathryn R. |
collection | PubMed |
description | Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. Drosophila offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type. We provide an overview of nucleolar stress in Drosophila by depleting nucleolar phosphoprotein of 140 kDa (Nopp140), a ribosome biogenesis factor (RBF) in nucleoli and Cajal bodies (CBs). The depletion of Nopp140 in eye imaginal disc cells generates eye deformities reminiscent of craniofacial deformities associated with the Treacher Collins syndrome (TCS), a human ribosomopathy. We show the activation of c-Jun N-terminal Kinase (JNK) in Drosophila larvae homozygous for a Nopp140 gene deletion. JNK is known to induce the expression of the pro-apoptotic Hid protein and autophagy factors Atg1, Atg18.1, and Atg8a; thus, JNK is a central regulator in Drosophila nucleolar stress. Ribosome abundance declines upon Nopp140 loss, but unusual cytoplasmic granules accumulate that resemble Processing (P) bodies based on marker proteins, Decapping Protein 1 (DCP1) and Maternal expression at 31B (Me31B). Wild type brain neuroblasts (NBs) express copious amounts of endogenous coilin, but coilin levels decline upon nucleolar stress in most NB types relative to the Mushroom body (MB) NBs. MB NBs exhibit resilience against nucleolar stress as they maintain normal coilin, Deadpan, and EdU labeling levels. |
format | Online Article Text |
id | pubmed-8267670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82676702021-07-10 Drosophila to Explore Nucleolar Stress DeLeo, Kathryn R. Baral, Sonu S. Houser, Alex James, Allison Sewell, Phelan Pandey, Shova DiMario, Patrick J. Int J Mol Sci Article Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. Drosophila offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type. We provide an overview of nucleolar stress in Drosophila by depleting nucleolar phosphoprotein of 140 kDa (Nopp140), a ribosome biogenesis factor (RBF) in nucleoli and Cajal bodies (CBs). The depletion of Nopp140 in eye imaginal disc cells generates eye deformities reminiscent of craniofacial deformities associated with the Treacher Collins syndrome (TCS), a human ribosomopathy. We show the activation of c-Jun N-terminal Kinase (JNK) in Drosophila larvae homozygous for a Nopp140 gene deletion. JNK is known to induce the expression of the pro-apoptotic Hid protein and autophagy factors Atg1, Atg18.1, and Atg8a; thus, JNK is a central regulator in Drosophila nucleolar stress. Ribosome abundance declines upon Nopp140 loss, but unusual cytoplasmic granules accumulate that resemble Processing (P) bodies based on marker proteins, Decapping Protein 1 (DCP1) and Maternal expression at 31B (Me31B). Wild type brain neuroblasts (NBs) express copious amounts of endogenous coilin, but coilin levels decline upon nucleolar stress in most NB types relative to the Mushroom body (MB) NBs. MB NBs exhibit resilience against nucleolar stress as they maintain normal coilin, Deadpan, and EdU labeling levels. MDPI 2021-06-23 /pmc/articles/PMC8267670/ /pubmed/34201772 http://dx.doi.org/10.3390/ijms22136759 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article DeLeo, Kathryn R. Baral, Sonu S. Houser, Alex James, Allison Sewell, Phelan Pandey, Shova DiMario, Patrick J. Drosophila to Explore Nucleolar Stress |
title | Drosophila to Explore Nucleolar Stress |
title_full | Drosophila to Explore Nucleolar Stress |
title_fullStr | Drosophila to Explore Nucleolar Stress |
title_full_unstemmed | Drosophila to Explore Nucleolar Stress |
title_short | Drosophila to Explore Nucleolar Stress |
title_sort | drosophila to explore nucleolar stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267670/ https://www.ncbi.nlm.nih.gov/pubmed/34201772 http://dx.doi.org/10.3390/ijms22136759 |
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