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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...

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Autores principales: Samaro, Alexia, Cristancho, Alejandra, Rivas, Alexis, Valtierra, Ruby, Beck, Skye, Cantu, Jason, Miranda, Maria, Vacio, Arianna, Cardenas Muedano, Oscar, Holgado, Andrea
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
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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.
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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
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