Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions

Cellular stress triggers the formation of diverse RNA–protein aggregates, which can be associated with physiological responses, pathological conditions, or even detrimental outcomes. Under stress-induced proteostasis disruption, these RNA–protein assemblies are known as stress granules (SGs). Target...

Descripción completa

Detalles Bibliográficos
Autores: Ramos Velasco, Beatriz, Alcalde, José, Izquierdo, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/401648
Acceso en línea:http://hdl.handle.net/10261/401648
Access Level:acceso abierto
Palabra clave:TIA1
Stress granules
Welander distal myopathy
Heat shock
Proteostatic insult
Oxidative stress
Osmotic challenge
id ES_2ea2e94b9a1fad320c8eff18f83ff527
oai_identifier_str oai:digital.csic.es:10261/401648
network_acronym_str ES
network_name_str España
repository_id_str
spelling Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress ConditionsRamos Velasco, BeatrizAlcalde, JoséIzquierdo, José M.TIA1Stress granulesWelander distal myopathyHeat shockProteostatic insultOxidative stressOsmotic challengeCellular stress triggers the formation of diverse RNA–protein aggregates, which can be associated with physiological responses, pathological conditions, or even detrimental outcomes. Under stress-induced proteostasis disruption, these RNA–protein assemblies are known as stress granules (SGs). Targeting such condensates—while sparing functional RNAs and proteins—remains a major therapeutic challenge in protein aggregation disorders such as myopathies and neuropathies. In this study, we investigated the cellular response to various stress conditions in the context of the TIA1 E384K mutation, a founder variant implicated in both Welander distal myopathy (WDM) and amyotrophic lateral sclerosis (ALS). Cells were exposed to different stressors, including proteotoxic, proteostatic, chemotoxic, and osmotic insults, and the behavior of TIA1-related SGs was analyzed. Our findings reveal a distinct yet conserved pattern in the dynamics of TIA1-dependent SG formation and clearance, influenced by the specific type of stressor and modulated by eIF2α Ser35 phosphorylation. These results indicate that the WDM-associated TIA1 mutation leads to aberrant SG dynamics across different stress conditions. Collectively, these observations support the idea that TIA1 E384K-associated SG dysregulation plays a role in WDM and ALS pathogenesis and underscores the importance of multiple stress contexts in disease progression.This work was supported by grants RTI2018-098517B-I00 and PID2021-126152OB-I00 from the ‘Ministerio de Ciencia, Innovación y Universidades’ and ‘Agencia Española de Investigación’ through FEDER funds (MICIU/AEI/FEDER, UE). B.R.-V. was supported by ‘Programa de Garantía Juvenil de la Comunidad de Madrid’ (GARJUVCAM-2020; Ref. 37722) and ‘Agencia Española de Investigación’ (PID2021-126152OB-I00). The CBM receives an institutional grant from the Fundación Ramón Areces, from MICIU/AEI/FEDER, UE.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Comunidad de MadridFundación Ramón ArecesEuropean CommissionIzquierdo, José M. [0000-0002-7942-4046]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/401648reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098517-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126152OB-I00GARJUVCAM-2020/37722info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126152OB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/biology14091288https://doi.org/10.3390/biology14091288Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4016482026-05-22T06:33:51Z
dc.title.none.fl_str_mv Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
title Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
spellingShingle Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
Ramos Velasco, Beatriz
TIA1
Stress granules
Welander distal myopathy
Heat shock
Proteostatic insult
Oxidative stress
Osmotic challenge
title_short Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
title_full Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
title_fullStr Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
title_full_unstemmed Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
title_sort Welander Distal Myopathy-Associated TIA1 E384K Mutation Disrupts Stress Granule Dynamics Under Distinct Stress Conditions
dc.creator.none.fl_str_mv Ramos Velasco, Beatriz
Alcalde, José
Izquierdo, José M.
author Ramos Velasco, Beatriz
author_facet Ramos Velasco, Beatriz
Alcalde, José
Izquierdo, José M.
author_role author
author2 Alcalde, José
Izquierdo, José M.
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Comunidad de Madrid
Fundación Ramón Areces
European Commission
Izquierdo, José M. [0000-0002-7942-4046]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv TIA1
Stress granules
Welander distal myopathy
Heat shock
Proteostatic insult
Oxidative stress
Osmotic challenge
topic TIA1
Stress granules
Welander distal myopathy
Heat shock
Proteostatic insult
Oxidative stress
Osmotic challenge
description Cellular stress triggers the formation of diverse RNA–protein aggregates, which can be associated with physiological responses, pathological conditions, or even detrimental outcomes. Under stress-induced proteostasis disruption, these RNA–protein assemblies are known as stress granules (SGs). Targeting such condensates—while sparing functional RNAs and proteins—remains a major therapeutic challenge in protein aggregation disorders such as myopathies and neuropathies. In this study, we investigated the cellular response to various stress conditions in the context of the TIA1 E384K mutation, a founder variant implicated in both Welander distal myopathy (WDM) and amyotrophic lateral sclerosis (ALS). Cells were exposed to different stressors, including proteotoxic, proteostatic, chemotoxic, and osmotic insults, and the behavior of TIA1-related SGs was analyzed. Our findings reveal a distinct yet conserved pattern in the dynamics of TIA1-dependent SG formation and clearance, influenced by the specific type of stressor and modulated by eIF2α Ser35 phosphorylation. These results indicate that the WDM-associated TIA1 mutation leads to aberrant SG dynamics across different stress conditions. Collectively, these observations support the idea that TIA1 E384K-associated SG dysregulation plays a role in WDM and ALS pathogenesis and underscores the importance of multiple stress contexts in disease progression.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/401648
url http://hdl.handle.net/10261/401648
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098517-B-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126152OB-I00
GARJUVCAM-2020/37722
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126152OB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/biology14091288
https://doi.org/10.3390/biology14091288
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405423223701504
score 15,812455

Similares en LA Referencia