Aß effects in protein phosphatase 1 complexes
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/21535 |
Resumo: | The brain is a complex structure, which is comprised by neurons capable of communication through synapses. These usually occur between an axon terminal and a dendritic spine of different neurons. The dendritic spines are dynamic structures that allow for a rapid adaptation to different stimuli. PP1 is a phosphatase protein that catalyses the majority of dephosphorylation reactions in the human body. It has different functions that vary, from glycogen metabolism to synaptic regulation. Neurabins (1 and 2) are two PP1 regulator subunits that are structurally and functionally similar to each other. They are highly enriched in the dendritic spines, interacting with several proteins, including PP1, and targeting them to receptors, cytoskeleton or other cellular compartments. Thus, regulating neuronal morphology and synaptic transmission and plasticity. Phactr3 belongs to the actin regulatory protein family, which comprises four members. Phactr3 is involved in cell migration and regulates cytoskeleton dynamics. It interacts with PP1 forming a complex that is controlled by changes in cytoplasmic G-actin concentration, thus, regulating actin cytoskeleton dynamics. Neurodegenerative diseases are usually characterised by the loss of synapses, neural death, gradual loss of cognitive functions and memory. It is believed that Aβ is the major culprit in these changes. Aβ results from an abnormal cleavage of APP, via the amyloidogenic pathway, resulting in the overproduction of toxic peptides. The main aim of this thesis was to evaluate the effects of Aβ on Neurabins and Phactr3 expression, and in PP1 complexes. The results show a slight decrease in neurabins’ expression, and a slight increase in Phactr3 expression. The results also show a decrease in interaction between PP1 and Neurabin-1, possibly due to direct effect of Aβ on Neurabin-1 or the imbalance of phosphatases and kinases, and between PP1 and Phactr3, possibly due to variations of G-actin levels which competes with PP1 to binding with Phactr3. The same changes were not observed in Neurabin-2/PP1 complexes. A possible explanation is that both are differently regulated by several kinases. The results allow us to conclude that Aβ interferes in the expression of all three proteins and in the interaction of Neurabin-1/PP1. However, additional studies are required in order to better understand the physiological relevance of these complexes. |
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Aß effects in protein phosphatase 1 complexesFosfatasesProteínasPéptidosThe brain is a complex structure, which is comprised by neurons capable of communication through synapses. These usually occur between an axon terminal and a dendritic spine of different neurons. The dendritic spines are dynamic structures that allow for a rapid adaptation to different stimuli. PP1 is a phosphatase protein that catalyses the majority of dephosphorylation reactions in the human body. It has different functions that vary, from glycogen metabolism to synaptic regulation. Neurabins (1 and 2) are two PP1 regulator subunits that are structurally and functionally similar to each other. They are highly enriched in the dendritic spines, interacting with several proteins, including PP1, and targeting them to receptors, cytoskeleton or other cellular compartments. Thus, regulating neuronal morphology and synaptic transmission and plasticity. Phactr3 belongs to the actin regulatory protein family, which comprises four members. Phactr3 is involved in cell migration and regulates cytoskeleton dynamics. It interacts with PP1 forming a complex that is controlled by changes in cytoplasmic G-actin concentration, thus, regulating actin cytoskeleton dynamics. Neurodegenerative diseases are usually characterised by the loss of synapses, neural death, gradual loss of cognitive functions and memory. It is believed that Aβ is the major culprit in these changes. Aβ results from an abnormal cleavage of APP, via the amyloidogenic pathway, resulting in the overproduction of toxic peptides. The main aim of this thesis was to evaluate the effects of Aβ on Neurabins and Phactr3 expression, and in PP1 complexes. The results show a slight decrease in neurabins’ expression, and a slight increase in Phactr3 expression. The results also show a decrease in interaction between PP1 and Neurabin-1, possibly due to direct effect of Aβ on Neurabin-1 or the imbalance of phosphatases and kinases, and between PP1 and Phactr3, possibly due to variations of G-actin levels which competes with PP1 to binding with Phactr3. The same changes were not observed in Neurabin-2/PP1 complexes. A possible explanation is that both are differently regulated by several kinases. The results allow us to conclude that Aβ interferes in the expression of all three proteins and in the interaction of Neurabin-1/PP1. However, additional studies are required in order to better understand the physiological relevance of these complexes.O cérebro é uma estrutura complexa, que é composta por neurónios capazes de comunicar através de sinapses. Estas normalmente ocorrem entre um terminal axónico e espinha dendritica de neurónios diferentes. As espinhas dendriticas são estruturas dinâmicas que permitem uma rápida adaptação a diferentes estímulos. A PP1 é uma proteína fosfatase que catalisa a maioria das desfosforilações que ocorrem no corpo humano. Tem diversas funções, que variam desde metabolismo de glicogénio a regulação sináptica. As neurorabinas (1 e 2) são duas subunidades reguladores da PP1 que são estruturalmente e funcionalmente idênticas entre si. São muito enriquecidas nas espinhas dendriticas e interagem com diversas proteínas, incluindo a PP1, e guiam as proteínas para receptores, citoesqueleto ou outros compartimentos celulares, regulando assim a morfologia neuronal e transmissão e plasticidade sináptica. A Phactr3 pertence à família de proteínas reguladoras de actina, á qual pertencem quatro membros. A Phactr3 está envolvida na migração celular e regula a dinâmica do citoesqueleto. Interage com a PP1, formando um complexo que é controlado por alterações na concentração de G-actina citoplasmática, regulando assim a dinâmica do citoesqueleto. Doenças neurodegenerativas, são normalmente caracterizadas pela perda de sinapses, morte neuronal, e perda gradual de funções cognitivas e memória. Acredita-se que o principal fator responsável por essas anomalias seja o péptido Aβ. Este resulta de uma clivagem anormal de APP, pela via amiloidogénica, resultando numa sobreprodução do péptido tóxico. O objectivo desta tese era avaliar os efeitos de Aβ nos níveis de expressão das neurorabinas e Phactr3, assim como os complexos formados com a PP1. Os resultados mostram uma ligeira diminuição nos níveis de expressão das neurorabinas, e num ligeiro aumento na expressão de Phactr3. Os resultados também mostram uma diminuição na interação do complexo Neurorabina-1/PP1, provavelmente devido a um efeito direto de Aβ sobre Neurorabina-1 ou um desequilíbrio nas fosfatases e cinases, e Phactr3/PP1, provavelmente devido a variação nos níveis de G-actina, que compete com a PP1 para interagir com Phactr3. As mesmas alterações não foram verificadas no complexo Neurorabina-2/PP1. Uma explicação possível é que ambas as proteínas são reguladas de forma diferente por diversas cinases. Estes resultados permitem concluir que Aβ interfere na expressão das três proteínas e nos níveis de interação de Neurabina-1/PP1 e Phactr3/PP1. No entanto são necessários mais estudos para obter uma melhor compreensão da relevância fisiológica destes complexos.Universidade de Aveiro2019-12-14T00:00:00Z2017-12-20T00:00:00Z2017-12-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/21535TID:201946408engJesus, João André Fernandes deinfo: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:RCAAP2024-05-06T04:11:23Zoai:ria.ua.pt:10773/21535Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-06T04:11:23Repositório 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 |
Aß effects in protein phosphatase 1 complexes |
title |
Aß effects in protein phosphatase 1 complexes |
spellingShingle |
Aß effects in protein phosphatase 1 complexes Jesus, João André Fernandes de Fosfatases Proteínas Péptidos |
title_short |
Aß effects in protein phosphatase 1 complexes |
title_full |
Aß effects in protein phosphatase 1 complexes |
title_fullStr |
Aß effects in protein phosphatase 1 complexes |
title_full_unstemmed |
Aß effects in protein phosphatase 1 complexes |
title_sort |
Aß effects in protein phosphatase 1 complexes |
author |
Jesus, João André Fernandes de |
author_facet |
Jesus, João André Fernandes de |
author_role |
author |
dc.contributor.author.fl_str_mv |
Jesus, João André Fernandes de |
dc.subject.por.fl_str_mv |
Fosfatases Proteínas Péptidos |
topic |
Fosfatases Proteínas Péptidos |
description |
The brain is a complex structure, which is comprised by neurons capable of communication through synapses. These usually occur between an axon terminal and a dendritic spine of different neurons. The dendritic spines are dynamic structures that allow for a rapid adaptation to different stimuli. PP1 is a phosphatase protein that catalyses the majority of dephosphorylation reactions in the human body. It has different functions that vary, from glycogen metabolism to synaptic regulation. Neurabins (1 and 2) are two PP1 regulator subunits that are structurally and functionally similar to each other. They are highly enriched in the dendritic spines, interacting with several proteins, including PP1, and targeting them to receptors, cytoskeleton or other cellular compartments. Thus, regulating neuronal morphology and synaptic transmission and plasticity. Phactr3 belongs to the actin regulatory protein family, which comprises four members. Phactr3 is involved in cell migration and regulates cytoskeleton dynamics. It interacts with PP1 forming a complex that is controlled by changes in cytoplasmic G-actin concentration, thus, regulating actin cytoskeleton dynamics. Neurodegenerative diseases are usually characterised by the loss of synapses, neural death, gradual loss of cognitive functions and memory. It is believed that Aβ is the major culprit in these changes. Aβ results from an abnormal cleavage of APP, via the amyloidogenic pathway, resulting in the overproduction of toxic peptides. The main aim of this thesis was to evaluate the effects of Aβ on Neurabins and Phactr3 expression, and in PP1 complexes. The results show a slight decrease in neurabins’ expression, and a slight increase in Phactr3 expression. The results also show a decrease in interaction between PP1 and Neurabin-1, possibly due to direct effect of Aβ on Neurabin-1 or the imbalance of phosphatases and kinases, and between PP1 and Phactr3, possibly due to variations of G-actin levels which competes with PP1 to binding with Phactr3. The same changes were not observed in Neurabin-2/PP1 complexes. A possible explanation is that both are differently regulated by several kinases. The results allow us to conclude that Aβ interferes in the expression of all three proteins and in the interaction of Neurabin-1/PP1. However, additional studies are required in order to better understand the physiological relevance of these complexes. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-12-20T00:00:00Z 2017-12-20 2019-12-14T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/21535 TID:201946408 |
url |
http://hdl.handle.net/10773/21535 |
identifier_str_mv |
TID:201946408 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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 |
Universidade de Aveiro |
publisher.none.fl_str_mv |
Universidade de Aveiro |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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 |
mluisa.alvim@gmail.com |
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1817543653525028864 |