TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins

Detalhes bibliográficos
Autor(a) principal: Fonseca-Gomes, João
Data de Publicação: 2019
Outros Autores: Jerónimo-Santos, André, Lesnikova, Angelina, Casarotto, Plinio, Castrén, Eero, Sebastião, Ana M, Diógenes, Maria José
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/54165
Resumo: Copyright © 2019 Fonseca-Gomes, Jerónimo-Santos, Lesnikova, Casarotto, Castrén, Sebastião and Diógenes. 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.
id RCAP_5f7868187cd7bef24ac0263f67f28dff
oai_identifier_str oai:repositorio.ul.pt:10451/54165
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteinsAlzheimer’s diseaseTrkB-FL cleavageTrkB-ICD fragmentBrain-derived neurotrophic factor (BDNF)ExcitotoxicityNeurodegenerationNeuroprotectionCopyright © 2019 Fonseca-Gomes, Jerónimo-Santos, Lesnikova, Casarotto, Castrén, Sebastião and Diógenes. 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.The signaling of brain-derived neurotrophic factor (BDNF) has been suggested to be impaired in Alzheimer's disease (AD), which may compromise the function of BDNF upon neuronal activity and survival. Accordingly, decreased levels of BDNF and its tropomyosin-receptor kinase B-full-length (TrkB-FL) have been detected in human brain samples of AD patients. We have previously found that neuronal exposure to amyloid-β (Aβ) peptide, a hallmark of AD, leads to calpain overactivation and subsequent TrkB-FL cleavage leading to decreased levels of TrkB-FL and the generation of two new fragments: a membrane-bound truncated receptor (TrkB-T') and an intracellular fragment (TrkB-ICD). Importantly, we identified this TrkB-FL cleavage and TrkB-ICD presence in human brain samples, which indicates that this molecular mechanism contributes to the loss of BDNF signaling in humans. The exact role of this TrkB-ICD fragment is, however, unknown. Here, we used a human neuroglioma cell line and rat cortical primary neuronal cultures to track TrkB-ICD intracellularly. Our data show that TrkB-ICD is a relatively stable fragment that accumulates in the nucleus over time, through a phosphorylation-dependent process. We also found that TrkB-ICD has tyrosine kinase activity, inducing the phosphorylation of nuclear and axonal proteins. These findings suggest that TrkB-ICD may lead to a dysregulation of the activity of several proteins, including proteins in the nucleus, to where TrkB-ICD migrates. Since TrkB-ICD is formed by Aβ peptide-induced cleavage of TrkB-FL, the present data highlights a new mechanism that may have a role in AD pathophysiology.Santa Casa da Misericórdia de Lisboa (MB37-2017); Fundação para a Ciência e a Tecnologia (FCT—PD/BD/114441/2016); SynaNet—Twinning Action funded by European Union’s H2020 (GA-692340) and UID/BIM/50005/2019, project financed by FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES), through Fundos do Orçamento de Estado. EC was supported by the ERC grant # 322742—iPLASTICITY, the Sigrid Jusélius foundation, the EU Joint Programme—Neurodegenerative Disease Research (JPND) project # JPCOFUND_FP-829-007, HiLife Fellows program, and Academy of Finland grants # 294710, 303124 and 307416.FrontiersRepositório da Universidade de LisboaFonseca-Gomes, JoãoJerónimo-Santos, AndréLesnikova, AngelinaCasarotto, PlinioCastrén, EeroSebastião, Ana MDiógenes, Maria José2022-08-23T10:27:34Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54165engFront Mol Neurosci. 2019 Feb 1;12:410.3389/fnmol.2019.000041662-5099info: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:RCAAP2023-11-08T16:59:43Zoai:repositorio.ul.pt:10451/54165Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:38.370519Repositório 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 TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
title TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
spellingShingle TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
Fonseca-Gomes, João
Alzheimer’s disease
TrkB-FL cleavage
TrkB-ICD fragment
Brain-derived neurotrophic factor (BDNF)
Excitotoxicity
Neurodegeneration
Neuroprotection
title_short TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
title_full TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
title_fullStr TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
title_full_unstemmed TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
title_sort TrkB-ICD fragment, originating from BDNF receptor cleavage, is translocated to cell nucleus and phosphorylates nuclear and axonal proteins
author Fonseca-Gomes, João
author_facet Fonseca-Gomes, João
Jerónimo-Santos, André
Lesnikova, Angelina
Casarotto, Plinio
Castrén, Eero
Sebastião, Ana M
Diógenes, Maria José
author_role author
author2 Jerónimo-Santos, André
Lesnikova, Angelina
Casarotto, Plinio
Castrén, Eero
Sebastião, Ana M
Diógenes, Maria José
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Fonseca-Gomes, João
Jerónimo-Santos, André
Lesnikova, Angelina
Casarotto, Plinio
Castrén, Eero
Sebastião, Ana M
Diógenes, Maria José
dc.subject.por.fl_str_mv Alzheimer’s disease
TrkB-FL cleavage
TrkB-ICD fragment
Brain-derived neurotrophic factor (BDNF)
Excitotoxicity
Neurodegeneration
Neuroprotection
topic Alzheimer’s disease
TrkB-FL cleavage
TrkB-ICD fragment
Brain-derived neurotrophic factor (BDNF)
Excitotoxicity
Neurodegeneration
Neuroprotection
description Copyright © 2019 Fonseca-Gomes, Jerónimo-Santos, Lesnikova, Casarotto, Castrén, Sebastião and Diógenes. 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
2022-08-23T10:27:34Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54165
url http://hdl.handle.net/10451/54165
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Mol Neurosci. 2019 Feb 1;12:4
10.3389/fnmol.2019.00004
1662-5099
dc.rights.driver.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 Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134597916655616

Registros relacionados