Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 25-03-2022

Detalles Bibliográficos
Autor: Fulgoni, Giulio
Tipo de recurso: tesis doctoral
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/702550
Acceso en línea:http://hdl.handle.net/10486/702550
Access Level:acceso abierto
Palabra clave:Proteínas
Mecanobiología
Células
Biología y Biomedicina / Biología
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spelling Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biologyPapel de RAB8 y Caveolina-1 en mecano-transducción celular y biología vascularFulgoni, GiulioProteínasMecanobiologíaCélulasBiología y Biomedicina / BiologíaTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 25-03-2022Esta tesis tiene embargado el acceso al texto completo hasta el 25-09-2023Mechanical forces are constantly generated during organ function and within tissues during cellular activities. Eukaryotic cells have evolved mechanotransduction pathways that allow them to sense physical stimuli and trigger adaptive responses, resulting in their functional reprogramming and the remodeling of the architecture of their extracellular environment. Recent research supports that these mechanoadaptive pathways, beyond protecting cells from physical damage, can profoundly impact cell behavior and affect the progression of complex diseases such as atherosclerosis. The thesis research reported here focuses on two proteins involved in cell mechanoadaption, specifically in the regulation of intracellular trafficking and plasma membrane (PM) organization: RAB8 and caveolin-1 (CAV1). A combination of different biophysical techniques has demonstrated that RAB8 localization is modulated by changes in PM tension or integrity, suggesting that specific RAB8 traffic pathways are activated in response to mechanical stimuli. In order to characterize the physiological role of RAB8 traffic in the vascular system, CRISPr-Cas9-edited endothelial cell lines were developed and tested in microfluidics systems. The data obtained indicates that RAB8 is required for the activation of flow shear stress mechanotransduction pathways, and for the regulation of CAV1 phosphorylation dynamics in response to flow. These results suggest that RAB8 may play a relevant role in endothelial homeostasis, and in the physiopathology of cardiovascular disorders such as atherosclerosis. Since RAB8 and CAV1 are both involved in lipid homeostasis and mechanoadaption, we hypothesized that intervening their expression would affect LDL transport in the endothelium in response to different mechanical conditions. To test that, in vitro assays were developed ad hoc to study the effect of substrate architecture and stiffness on LDL trafficking and retention. While our observations were not conclusive regarding the specific involvement of RAB8 or CAV1 in the coupling of substrate sensing and LDL management, these optimized, quantitative in vitro assays offer a versatile opportunity for the detailed study of the different phases of LDL transport that occurs in blood vessels during atherosclerosis progressionPozo Barriuso, Miguel Ángel delMontoya Sánchez, MaríaDepartamento de Biología MolecularFacultad de CienciasCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)20222022-03-25doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/702550reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7025502026-06-23T12:46:27Z
dc.title.none.fl_str_mv Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
Papel de RAB8 y Caveolina-1 en mecano-transducción celular y biología vascular
title Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
spellingShingle Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
Fulgoni, Giulio
Proteínas
Mecanobiología
Células
Biología y Biomedicina / Biología
title_short Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
title_full Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
title_fullStr Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
title_full_unstemmed Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
title_sort Role of RAB8 and Caveolin-1 in cell mechanotransduction and vascular biology
dc.creator.none.fl_str_mv Fulgoni, Giulio
author Fulgoni, Giulio
author_facet Fulgoni, Giulio
author_role author
dc.contributor.none.fl_str_mv Pozo Barriuso, Miguel Ángel del
Montoya Sánchez, María
Departamento de Biología Molecular
Facultad de Ciencias
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
dc.subject.none.fl_str_mv Proteínas
Mecanobiología
Células
Biología y Biomedicina / Biología
topic Proteínas
Mecanobiología
Células
Biología y Biomedicina / Biología
description Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de Lectura: 25-03-2022
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-03-25
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/702550
url http://hdl.handle.net/10486/702550
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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