Cargando…
The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants
Collapsin response mediator protein-2 (CRMP2) in humans, UNC-33 in C. elegans, is a molecule that mediates axonal outgrowth and stability. UNC-33/CRMP2 has been hypothesized as a potential drug target for treating Alzheimer’s and other neurodegenerative diseases, which can often be attributed in par...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9939912/ https://www.ncbi.nlm.nih.gov/pubmed/36814478 http://dx.doi.org/10.3389/fphys.2023.975878 |
_version_ | 1784890967556358144 |
---|---|
author | Samaro, Alexia Cristancho, Alejandra Rivas, Alexis Valtierra, Ruby Beck, Skye Cantu, Jason Miranda, Maria Vacio, Arianna Cardenas Muedano, Oscar Holgado, Andrea |
author_facet | Samaro, Alexia Cristancho, Alejandra Rivas, Alexis Valtierra, Ruby Beck, Skye Cantu, Jason Miranda, Maria Vacio, Arianna Cardenas Muedano, Oscar Holgado, Andrea |
author_sort | Samaro, Alexia |
collection | PubMed |
description | Collapsin response mediator protein-2 (CRMP2) in humans, UNC-33 in C. elegans, is a molecule that mediates axonal outgrowth and stability. UNC-33/CRMP2 has been hypothesized as a potential drug target for treating Alzheimer’s and other neurodegenerative diseases, which can often be attributed in part to aging. In aging, CRMP2 becomes hyperphosphorylated, which decreases the protein’s functionality, destabilizes the cellular skeleton, and contributes to neurodegeneration. In C. elegans, aging can be slowed by entering dauer diapause; a non-aging developmental stage turned on when the DAF-7/TGFβ signaling pathway is silenced in response to environmental stressors. In our laboratory, we discovered that unc-33 mutants are unable to form dauers in response to environmental stressors, but the mechanism behind this is still unknown. Here, we present a study that investigates whether a mutation in the daf-7 gene which leads to a temperature sensitive constitutive dauer phenotype can rescue phenotypes characteristic of unc-33 mutants. To this end, we created unc-33; daf-7 double mutants and quantified proper dauer formation after exposure to unfavorable environmental conditions. In addition, we tested how the introduction of the daf-7 mutation would affect the locomotion of the double mutants on an agar plate and a liquid medium. Furthermore, we examined axonal elongation of the double mutants using a transgene, juIs76, which expresses GFP in GABAergic motor neurons. Our analysis of unc-33; daf-7 double mutants showed that introducing the daf-7 mutation into an unc-33 mutant rescued dauer formation. However, further studies revealed that the unc-33; daf-7 double mutants had defects in axonal outgrowth of their D-type motor neuron which had been previously seen in unc-33 single mutants and impaired locomotion. Based on these results, we concluded that unc-33 mutants might have a problem suppressing DAF-7 signaling under unfavorable environmental conditions, leading to the activation of reproductive programs and the development of adults instead of dauers. |
format | Online Article Text |
id | pubmed-9939912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99399122023-02-21 The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants Samaro, Alexia Cristancho, Alejandra Rivas, Alexis Valtierra, Ruby Beck, Skye Cantu, Jason Miranda, Maria Vacio, Arianna Cardenas Muedano, Oscar Holgado, Andrea Front Physiol Physiology Collapsin response mediator protein-2 (CRMP2) in humans, UNC-33 in C. elegans, is a molecule that mediates axonal outgrowth and stability. UNC-33/CRMP2 has been hypothesized as a potential drug target for treating Alzheimer’s and other neurodegenerative diseases, which can often be attributed in part to aging. In aging, CRMP2 becomes hyperphosphorylated, which decreases the protein’s functionality, destabilizes the cellular skeleton, and contributes to neurodegeneration. In C. elegans, aging can be slowed by entering dauer diapause; a non-aging developmental stage turned on when the DAF-7/TGFβ signaling pathway is silenced in response to environmental stressors. In our laboratory, we discovered that unc-33 mutants are unable to form dauers in response to environmental stressors, but the mechanism behind this is still unknown. Here, we present a study that investigates whether a mutation in the daf-7 gene which leads to a temperature sensitive constitutive dauer phenotype can rescue phenotypes characteristic of unc-33 mutants. To this end, we created unc-33; daf-7 double mutants and quantified proper dauer formation after exposure to unfavorable environmental conditions. In addition, we tested how the introduction of the daf-7 mutation would affect the locomotion of the double mutants on an agar plate and a liquid medium. Furthermore, we examined axonal elongation of the double mutants using a transgene, juIs76, which expresses GFP in GABAergic motor neurons. Our analysis of unc-33; daf-7 double mutants showed that introducing the daf-7 mutation into an unc-33 mutant rescued dauer formation. However, further studies revealed that the unc-33; daf-7 double mutants had defects in axonal outgrowth of their D-type motor neuron which had been previously seen in unc-33 single mutants and impaired locomotion. Based on these results, we concluded that unc-33 mutants might have a problem suppressing DAF-7 signaling under unfavorable environmental conditions, leading to the activation of reproductive programs and the development of adults instead of dauers. Frontiers Media S.A. 2023-02-06 /pmc/articles/PMC9939912/ /pubmed/36814478 http://dx.doi.org/10.3389/fphys.2023.975878 Text en Copyright © 2023 Samaro, Cristancho, Rivas, Valtierra, Beck, Cantu, Miranda, Vacio, Cardenas Muedano and Holgado. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Samaro, Alexia Cristancho, Alejandra Rivas, Alexis Valtierra, Ruby Beck, Skye Cantu, Jason Miranda, Maria Vacio, Arianna Cardenas Muedano, Oscar Holgado, Andrea The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants |
title | The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants |
title_full | The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants |
title_fullStr | The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants |
title_full_unstemmed | The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants |
title_short | The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants |
title_sort | daf-7(e1372) mutation rescues dauer formation defects seen in c. elegans unc-33 mutants |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9939912/ https://www.ncbi.nlm.nih.gov/pubmed/36814478 http://dx.doi.org/10.3389/fphys.2023.975878 |
work_keys_str_mv | AT samaroalexia thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT cristanchoalejandra thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT rivasalexis thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT valtierraruby thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT beckskye thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT cantujason thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT mirandamaria thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT vacioarianna thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT cardenasmuedanooscar thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT holgadoandrea thedaf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT samaroalexia daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT cristanchoalejandra daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT rivasalexis daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT valtierraruby daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT beckskye daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT cantujason daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT mirandamaria daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT vacioarianna daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT cardenasmuedanooscar daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants AT holgadoandrea daf7e1372mutationrescuesdauerformationdefectsseenincelegansunc33mutants |