Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1)
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/144960 |
Resumo: | Funding Information: This research was supported by the Isabel Gemio Foundation (P18–13) and was also partially supported by the “Fondo Europeo de Desarrollo Regional” (FEDER) from the European Union. E.A.-C. was supported by a pre-doctoral fellowship of Valhondo Calaff Foundation. S.C.-C. and E.U.-C. were supported by FPU fellowships (FPU19/04435 and FPU16/00684, respectively) from the Ministerio de Ciencia, Innovación y Universidades, Spain. M.P.-B. and A.G.-B. received fellowships from the “Plan Propio de Iniciación a la Investigación, Desarrollo Tecnológico e Innovación (Universidad de Extremadura). M.N.-S. was supported by the “Ramon y Cajal” Program (RYC-2016–20883), and P.G.-S., was funded by “Juan de la Cierva Incorporación” Program (IJC2019–039229-I), Spain. S.M.S.Y.-D. was supported by the Isabel Gemio Foundation and CIBERNED (CB06/05/0041). J.M.F received research support from the Isabel Gemio Foundation and the “Instituto de Salud Carlos” III, CIBERNED (CB06/05/0041). Publisher Copyright: © 2022 by the authors. |
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Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1)AKTautophagyDMPKendosomesLBPAlysosomesmuscle atrophyBiochemistry, Genetics and Molecular Biology(all)Funding Information: This research was supported by the Isabel Gemio Foundation (P18–13) and was also partially supported by the “Fondo Europeo de Desarrollo Regional” (FEDER) from the European Union. E.A.-C. was supported by a pre-doctoral fellowship of Valhondo Calaff Foundation. S.C.-C. and E.U.-C. were supported by FPU fellowships (FPU19/04435 and FPU16/00684, respectively) from the Ministerio de Ciencia, Innovación y Universidades, Spain. M.P.-B. and A.G.-B. received fellowships from the “Plan Propio de Iniciación a la Investigación, Desarrollo Tecnológico e Innovación (Universidad de Extremadura). M.N.-S. was supported by the “Ramon y Cajal” Program (RYC-2016–20883), and P.G.-S., was funded by “Juan de la Cierva Incorporación” Program (IJC2019–039229-I), Spain. S.M.S.Y.-D. was supported by the Isabel Gemio Foundation and CIBERNED (CB06/05/0041). J.M.F received research support from the Isabel Gemio Foundation and the “Instituto de Salud Carlos” III, CIBERNED (CB06/05/0041). Publisher Copyright: © 2022 by the authors.Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. Autophagy has been widely studied in DM1, although the endocytic pathway has not. AKT has a critical role in endocytosis, and its phosphorylation is mediated by the activation of tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR). EGF-activated EGFR triggers the internalization and degradation of ligand–receptor complexes that serve as a PI3K/AKT signaling platform. Here, we used primary fibroblasts from healthy subjects and DM1 patients. DM1-derived fibroblasts showed increased autophagy flux, with enlarged endosomes and lysosomes. Thereafter, cells were stimulated with a high concentration of EGF to promote EGFR internalization and degradation. Interestingly, EGF binding to EGFR was reduced in DM1 cells and EGFR internalization was also slowed during the early steps of endocytosis. However, EGF-activated EGFR enhanced AKT and ERK1/2 phosphorylation levels in the DM1-derived fibroblasts. Therefore, there was a delay in EGF-stimulated EGFR endocytosis in DM1 cells; this alteration might be due to the decrease in the binding of EGF to EGFR, and not to a decrease in AKT phosphorylation.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSRUNAlegre-Cortés, EvaGiménez-Bejarano, AlbertoUribe-Carretero, ElisabetParedes-Barquero, MartaMarques, André R.A.Lopes-da-Silva, MafaldaVieira, Otília V.Canales-Cortés, SarayCamello, Pedro J.Martínez-Chacón, GuadalupeAiastui, AnaFernández-Torrón, RobertoLópez de Munain, AdolfoGomez-Suaga, PatriciaNiso-Santano, MireiaGonzález-Polo, Rosa A.Fuentes, José M.Yakhine-Diop, Sokhna M.S.2022-10-24T22:13:32Z2022-102022-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/144960eng2073-4409PURE: 47284498https://doi.org/10.3390/cells11193018info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-22T18:06:10Zoai:run.unl.pt:10362/144960Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:06:10Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| title |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| spellingShingle |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) Alegre-Cortés, Eva AKT autophagy DMPK endosomes LBPA lysosomes muscle atrophy Biochemistry, Genetics and Molecular Biology(all) |
| title_short |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| title_full |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| title_fullStr |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| title_full_unstemmed |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| title_sort |
Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) |
| author |
Alegre-Cortés, Eva |
| author_facet |
Alegre-Cortés, Eva Giménez-Bejarano, Alberto Uribe-Carretero, Elisabet Paredes-Barquero, Marta Marques, André R.A. Lopes-da-Silva, Mafalda Vieira, Otília V. Canales-Cortés, Saray Camello, Pedro J. Martínez-Chacón, Guadalupe Aiastui, Ana Fernández-Torrón, Roberto López de Munain, Adolfo Gomez-Suaga, Patricia Niso-Santano, Mireia González-Polo, Rosa A. Fuentes, José M. Yakhine-Diop, Sokhna M.S. |
| author_role |
author |
| author2 |
Giménez-Bejarano, Alberto Uribe-Carretero, Elisabet Paredes-Barquero, Marta Marques, André R.A. Lopes-da-Silva, Mafalda Vieira, Otília V. Canales-Cortés, Saray Camello, Pedro J. Martínez-Chacón, Guadalupe Aiastui, Ana Fernández-Torrón, Roberto López de Munain, Adolfo Gomez-Suaga, Patricia Niso-Santano, Mireia González-Polo, Rosa A. Fuentes, José M. Yakhine-Diop, Sokhna M.S. |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS RUN |
| dc.contributor.author.fl_str_mv |
Alegre-Cortés, Eva Giménez-Bejarano, Alberto Uribe-Carretero, Elisabet Paredes-Barquero, Marta Marques, André R.A. Lopes-da-Silva, Mafalda Vieira, Otília V. Canales-Cortés, Saray Camello, Pedro J. Martínez-Chacón, Guadalupe Aiastui, Ana Fernández-Torrón, Roberto López de Munain, Adolfo Gomez-Suaga, Patricia Niso-Santano, Mireia González-Polo, Rosa A. Fuentes, José M. Yakhine-Diop, Sokhna M.S. |
| dc.subject.por.fl_str_mv |
AKT autophagy DMPK endosomes LBPA lysosomes muscle atrophy Biochemistry, Genetics and Molecular Biology(all) |
| topic |
AKT autophagy DMPK endosomes LBPA lysosomes muscle atrophy Biochemistry, Genetics and Molecular Biology(all) |
| description |
Funding Information: This research was supported by the Isabel Gemio Foundation (P18–13) and was also partially supported by the “Fondo Europeo de Desarrollo Regional” (FEDER) from the European Union. E.A.-C. was supported by a pre-doctoral fellowship of Valhondo Calaff Foundation. S.C.-C. and E.U.-C. were supported by FPU fellowships (FPU19/04435 and FPU16/00684, respectively) from the Ministerio de Ciencia, Innovación y Universidades, Spain. M.P.-B. and A.G.-B. received fellowships from the “Plan Propio de Iniciación a la Investigación, Desarrollo Tecnológico e Innovación (Universidad de Extremadura). M.N.-S. was supported by the “Ramon y Cajal” Program (RYC-2016–20883), and P.G.-S., was funded by “Juan de la Cierva Incorporación” Program (IJC2019–039229-I), Spain. S.M.S.Y.-D. was supported by the Isabel Gemio Foundation and CIBERNED (CB06/05/0041). J.M.F received research support from the Isabel Gemio Foundation and the “Instituto de Salud Carlos” III, CIBERNED (CB06/05/0041). Publisher Copyright: © 2022 by the authors. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-10-24T22:13:32Z 2022-10 2022-10-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/144960 |
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http://hdl.handle.net/10362/144960 |
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eng |
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eng |
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2073-4409 PURE: 47284498 https://doi.org/10.3390/cells11193018 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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mluisa.alvim@gmail.com |
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