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RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila
TDP-43 is an ubiquitous and highly conserved ribonucleoprotein involved in several cellular processes including pre-mRNA splicing, transcription, mRNA stability and transport. Notwithstanding the evidence of TDP-43 involvement in the pathogenesis of different neurodegenerative disorders (i.e. ALS an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898758/ https://www.ncbi.nlm.nih.gov/pubmed/29652933 http://dx.doi.org/10.1371/journal.pone.0195845 |
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author | Langellotti, Simona Romano, Giulia Feiguin, Fabian Baralle, Francisco Ernesto Romano, Maurizio |
author_facet | Langellotti, Simona Romano, Giulia Feiguin, Fabian Baralle, Francisco Ernesto Romano, Maurizio |
author_sort | Langellotti, Simona |
collection | PubMed |
description | TDP-43 is an ubiquitous and highly conserved ribonucleoprotein involved in several cellular processes including pre-mRNA splicing, transcription, mRNA stability and transport. Notwithstanding the evidence of TDP-43 involvement in the pathogenesis of different neurodegenerative disorders (i.e. ALS and FTLD), the underlying mechanisms are still unclear. Given the high degree of functional similarity between the human and fly orthologs of TDP-43, Drosophila melanogaster is a simple and useful model to study the pathophysiological role of this protein in vivo. It has been demonstrated that the depletion of the TDP-43 fly ortholog (tbph) induces deficient locomotive behaviors and reduces life span and anatomical defects at the neuromuscular junction. In this study, using the known binding specificity of TDP-43/tbph for (UG) repeated sequences, we performed a bioinformatic screening for fly genes with at least 6 (TG) repeats in a row within the 3'-UTR regions in order to identify the genes that might be regulated by this factor. Among these genes, we were able to identify RhoGAPp190 as a potential target of the tbph-mediated neurodegeneration. RhoGAPp190 is a negative regulator of Drosophila RhoA, a GTPase protein implicated in the fine modulation of critical cellular processes including axon branch stability and motor axon defasciculation at muscle level and cognitive processes. We were able to demonstrate that the RhoGAPp190 expression is upregulated in a tbph-null fly model, providing evidence that this deregulation is associated to tbph silencing. Our results introduce RhoGAPp190 as a novel potential mediator in the complex scenario of events resulting from in vivo tbph loss-of-function. |
format | Online Article Text |
id | pubmed-5898758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58987582018-04-27 RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila Langellotti, Simona Romano, Giulia Feiguin, Fabian Baralle, Francisco Ernesto Romano, Maurizio PLoS One Research Article TDP-43 is an ubiquitous and highly conserved ribonucleoprotein involved in several cellular processes including pre-mRNA splicing, transcription, mRNA stability and transport. Notwithstanding the evidence of TDP-43 involvement in the pathogenesis of different neurodegenerative disorders (i.e. ALS and FTLD), the underlying mechanisms are still unclear. Given the high degree of functional similarity between the human and fly orthologs of TDP-43, Drosophila melanogaster is a simple and useful model to study the pathophysiological role of this protein in vivo. It has been demonstrated that the depletion of the TDP-43 fly ortholog (tbph) induces deficient locomotive behaviors and reduces life span and anatomical defects at the neuromuscular junction. In this study, using the known binding specificity of TDP-43/tbph for (UG) repeated sequences, we performed a bioinformatic screening for fly genes with at least 6 (TG) repeats in a row within the 3'-UTR regions in order to identify the genes that might be regulated by this factor. Among these genes, we were able to identify RhoGAPp190 as a potential target of the tbph-mediated neurodegeneration. RhoGAPp190 is a negative regulator of Drosophila RhoA, a GTPase protein implicated in the fine modulation of critical cellular processes including axon branch stability and motor axon defasciculation at muscle level and cognitive processes. We were able to demonstrate that the RhoGAPp190 expression is upregulated in a tbph-null fly model, providing evidence that this deregulation is associated to tbph silencing. Our results introduce RhoGAPp190 as a novel potential mediator in the complex scenario of events resulting from in vivo tbph loss-of-function. Public Library of Science 2018-04-13 /pmc/articles/PMC5898758/ /pubmed/29652933 http://dx.doi.org/10.1371/journal.pone.0195845 Text en © 2018 Langellotti et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Langellotti, Simona Romano, Giulia Feiguin, Fabian Baralle, Francisco Ernesto Romano, Maurizio RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila |
title | RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila |
title_full | RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila |
title_fullStr | RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila |
title_full_unstemmed | RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila |
title_short | RhoGAPp190: A potential player in tbph-mediated neurodegeneration in Drosophila |
title_sort | rhogapp190: a potential player in tbph-mediated neurodegeneration in drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898758/ https://www.ncbi.nlm.nih.gov/pubmed/29652933 http://dx.doi.org/10.1371/journal.pone.0195845 |
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