Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal

Programa de Doctorat en Biomedicina

Detalles Bibliográficos
Autor: Ortega Gascó, Alba
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/689066
Acceso en línea:http://hdl.handle.net/10803/689066
Access Level:acceso abierto
Palabra clave:Neurobiologia del desenvolupament
Neurobiología del desarrollo
Developmental neurobiology
Neuroplasticitat
Neuroplasticidad
Neuroplasticity
Morfogènesi
Morfogénesis
Morphogenesis
Hipocamp (Cervell)
Hipocampo (Cerebro)
Hippocampus (Brain)
Proteïnes
Proteínas
Proteins
Ciències Experimentals i Matemàtiques
616.8
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oai_identifier_str oai:www.tdx.cat:10803/689066
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
title Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
spellingShingle Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
Ortega Gascó, Alba
Neurobiologia del desenvolupament
Neurobiología del desarrollo
Developmental neurobiology
Neuroplasticitat
Neuroplasticidad
Neuroplasticity
Morfogènesi
Morfogénesis
Morphogenesis
Hipocamp (Cervell)
Hipocampo (Cerebro)
Hippocampus (Brain)
Proteïnes
Proteínas
Proteins
Ciències Experimentals i Matemàtiques
616.8
title_short Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
title_full Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
title_fullStr Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
title_full_unstemmed Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
title_sort Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronal
dc.creator.none.fl_str_mv Ortega Gascó, Alba
author Ortega Gascó, Alba
author_facet Ortega Gascó, Alba
author_role author
dc.contributor.none.fl_str_mv Soriano García, Eduardo
Pujadas Puigdomènech, Lluís
Soriano García, Eduardo
Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia
dc.subject.none.fl_str_mv Neurobiologia del desenvolupament
Neurobiología del desarrollo
Developmental neurobiology
Neuroplasticitat
Neuroplasticidad
Neuroplasticity
Morfogènesi
Morfogénesis
Morphogenesis
Hipocamp (Cervell)
Hipocampo (Cerebro)
Hippocampus (Brain)
Proteïnes
Proteínas
Proteins
Ciències Experimentals i Matemàtiques
616.8
topic Neurobiologia del desenvolupament
Neurobiología del desarrollo
Developmental neurobiology
Neuroplasticitat
Neuroplasticidad
Neuroplasticity
Morfogènesi
Morfogénesis
Morphogenesis
Hipocamp (Cervell)
Hipocampo (Cerebro)
Hippocampus (Brain)
Proteïnes
Proteínas
Proteins
Ciències Experimentals i Matemàtiques
616.8
description Programa de Doctorat en Biomedicina
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/689066
url http://hdl.handle.net/10803/689066
dc.language.none.fl_str_mv Catalán
language_invalid_str_mv Catalán
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 261 p.
application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404221238935552
spelling Anàlisi de les funcions de la proteïna NCAM2 en desenvolupament i plasticitat neuronalOrtega Gascó, AlbaNeurobiologia del desenvolupamentNeurobiología del desarrolloDevelopmental neurobiologyNeuroplasticitatNeuroplasticidadNeuroplasticityMorfogènesiMorfogénesisMorphogenesisHipocamp (Cervell)Hipocampo (Cerebro)Hippocampus (Brain)ProteïnesProteínasProteinsCiències Experimentals i Matemàtiques616.8Programa de Doctorat en Biomedicina[eng] The Central Nervous System (NS) is a fascinating and complex structure formed by millions of interconnected neurons that facilitate cognitive tasks such as memory and learning. The development and maintenance of this system rely on genetic programs that regulate the spatial and temporal expression of numerous genes. Cell adhesion molecules (CAMs) are key proteins in the development and maintenance of the adult CNS participating in the architecture of the system and in signal transduction. These proteins exhibit a wide range of structural and functional diversity, allowing them to regulate different processes, including the renewal and proliferation of neural stem cells (NSCs), neuronal migration and differentiation, as well as the integration of neurons into functional circuits. The present thesis investigates the role of neuronal cell adhesion molecule 2 (NCAM2) in neuronal development and the regulation of adult neuronal plasticity. NCAM2, also known as OCAM and RNCAM, is a glycoprotein located in the cell membrane from the NCAM family. The NCAM family comprises two members, NCAM1 and NCAM2, which are generated by genomic duplication. Alternative splicing of Ncam2 produces two isoforms of the protein: NCAM2.1 and NCAM2.2. Both isoforms share an extracellular domain composed of five immunoglobulin-like modules (IgI-IgV) and two fibronectin type III modules (FnIII1-2). Through the extracellular domain, they establish trans homophilic interactions that are responsible for a large part of their functions. The intracellular domain varies depending on the isoform, while NCAM2.1 has a transmembrane domain and a cytoplasmic tail, NCAM2.2 is attached to the membrane via a glycosylphosphatidylinositol (GPI) anchor. The different structure of the isoforms diversifies their cellular localization, interactions, and biological functions. The implications of NCAM2 have been extensively studied in the olfactory bulb, where it participates in neurite growth, axo-dendritic compartmentalization, and selective axon fasciculation. However, its role outside of this region largely unexplored to date. The main objective of this thesis has been to determine the functions of the NCAM2 protein in the cortex and hippocampus. It has been observed that NCAM2 controls the process of neuronal polarization and morphogenesis. Silencing the protein during neuronal polarization events leads to aberrant dendritic phenotypes and the formation of shorter and more branched axons. The mechanisms through which NCAM2 mediates its functions in neuronal morphogenesis include interaction with cytoskeletal proteins (actin, tubulin, and neurofilaments), cytoskeleton-associated proteins (MAP1B, MAP2, or CAPZ), and other intercellular effectors (CAMKII or 14-3-3). Moreover, the effect of the NCAM2 protein on the regulation of adult neural stem cells (NSCs) and synaptic plasticity in the hippocampus has been analyzed. The results in the context of neurogenesis revealed that regulated levels of Ncam2 are necessary for the proper activation of quiescent NSCs, their division, and neuronal differentiation. Increased levels of NCAM2 lead to cell arrest at a neural progenitor stage and hinder the formation of new neurons. In synaptic plasticity, our data show that the protein is necessary for synaptic formation and its proper maintenance during adulthood. Silencing NCAM2 leads to a constriction and a reduction in density of spines. Conversely, upregulated levels may promote contact stabilization by increasing the size of dendritic spines. In summary, the results obtained in this thesis highlight the relevance of NCAM2 in neuronal development and plasticity, thus reinforcing the crucial role of CAMs in the proper functioning of the CNS. The NCAM2 gene has been associated with neurodevelopmental disorders or neurodegenerative diseases such as autism, Down syndrome, or Alzheimer's disease. The evidence provided in the thesis, could enhance our understanding of the neurogenic and synaptic deficits that occur in these pathologies and opening new promising avenues for future research.Universitat de BarcelonaSoriano García, EduardoPujadas Puigdomènech, LluísSoriano García, EduardoUniversitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia202320242023info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion261 p.application/pdfhttp://hdl.handle.net/10803/689066TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCACatalánADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6890662026-06-14T12:46:07Z
score 15,81155

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