Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease

Detalhes bibliográficos
Autor(a) principal: Lérias, Joana Ramos Rapaz, 1988-
Data de Publicação: 2018
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10451/35037
Resumo: Tese de doutoramento, Biologia (Biologia de Sistemas), Universidade de Lisboa, Faculdade de Ciências, 2018
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spelling Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in diseaseTeses de doutoramento - 2018Domínio/Área Científica::Ciências Naturais::Ciências BiológicasTese de doutoramento, Biologia (Biologia de Sistemas), Universidade de Lisboa, Faculdade de Ciências, 2018Cystic fibrosis (CF), the most common life-shortening autosomal recessive disorder in Caucasians, is caused by >2,000 different mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR). CFTR is a Cl- and HCO3- permeant channel expressed in the epithelial apical membrane. Clinically, the majority of CF patients suffer mostly from severe lung disease. A possible approach to treat CF is through the stimulation of alternative channels, such as anoctamins, that could compensate for absence of CFTR mediated Cl- secretion, thus being called “bypass” approach. The prime objective of this PhD project focusses on identifying novel anoctamin regulators as possible drug targets for CF. The first chapter describes the generation of CFBE-3HA-ANO1-eGFP cells and their use in a siRNA traffic screen. As a result, nine hits were selected for functional validation: Extended Synaptotagmin Member 1 (ESYT1) and Casein Kinase 2 (CSNK2) as negative modulators and Peptidoglycan Recognition Protein 3 (PGLYRP3) and Coat Protein Complex I subunit β1 (COPβ1) as positive hits. These screen data also showed a positive regulation of ANO1 by GPCRs, which were further characterized in chapter two. Our data illustrate an overlap between Ca2+- and cAMP- induced currents, which prevent a clear distinction between their respective Cl- currents. Our data in the third chapter describes the relationship between ANO1 and mucus and show that IL4 treatment (an inducer of ANO1 expression) does not affect MUC5AC levels, in contrast to other studies which proposed a causative role for ANO1 in mucus production. In the fourth chapter, the relationship between ANO1, ANO6 and CFTR was further investigated and our data suggest that CFTR activation requires at least one anoctamin member trafficking to the PM, to probably modulate cellular Ca2+ signalling and activate CFTR by SOcAMPs and Ca2+-sensitive adenylyl cyclases.Fundação para a Ciência e a Tecnologia (FCT), SFRH/BD/52489/2014Kunzelmann, Karl, 1958-Amaral, Margarida, 1958-Repositório da Universidade de LisboaLérias, Joana Ramos Rapaz, 1988-2018-10-12T16:03:18Z201820182018-01-01T00:00:00Zdoctoral thesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10451/35037TID:101508824enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T13:58:01Zoai:repositorio.ulisboa.pt:10451/35037Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T02:59:13.883758Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
title Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
spellingShingle Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
Lérias, Joana Ramos Rapaz, 1988-
Teses de doutoramento - 2018
Domínio/Área Científica::Ciências Naturais::Ciências Biológicas
title_short Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
title_full Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
title_fullStr Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
title_full_unstemmed Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
title_sort Anoctamin 1-A member of a novel family of ion channels with extended functions and significance in disease
author Lérias, Joana Ramos Rapaz, 1988-
author_facet Lérias, Joana Ramos Rapaz, 1988-
author_role author
dc.contributor.none.fl_str_mv Kunzelmann, Karl, 1958-
Amaral, Margarida, 1958-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Lérias, Joana Ramos Rapaz, 1988-
dc.subject.por.fl_str_mv Teses de doutoramento - 2018
Domínio/Área Científica::Ciências Naturais::Ciências Biológicas
topic Teses de doutoramento - 2018
Domínio/Área Científica::Ciências Naturais::Ciências Biológicas
description Tese de doutoramento, Biologia (Biologia de Sistemas), Universidade de Lisboa, Faculdade de Ciências, 2018
publishDate 2018
dc.date.none.fl_str_mv 2018-10-12T16:03:18Z
2018
2018
2018-01-01T00:00:00Z
dc.type.driver.fl_str_mv doctoral thesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/35037
TID:101508824
url http://hdl.handle.net/10451/35037
identifier_str_mv TID:101508824
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.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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