Publicação
Dissecting the role of ral gtpase in neuronal and glial Structure and function
| Resumo: | Abstract The complexity of the nervous system demands and relies on a diversity of molecular processes essential for its correct development and functioning. Coordinated growth and communication between neurons and glia is crucial and indispensable for the physiological functions of the nervous system. Balanced neuronal and glial interaction and communication is decisive, for instance, to ensure suitable axonal insulation and fasciculation. Axonal ensheathment and insulation are critical for fast and reliable impulse conduction and disturbances in these processes often result in highly debilitating disorders, such as multiple sclerosis. Despite the obvious importance, our knowledge regarding the molecular players responsible for controlling the development, growth and communication between neurons and glia is still somewhat limited. In my thesis, we identified RalA GTPase and the exocyst complex as key regulators of axonal ensheathment in Drosophila melanogaster larval peripheral nerves. Detailed genetic analysis showed that RalA is required for wrapping glia growth and development, acting together with its effector exocyst. Our data suggests that this mechanism is regulated through the activation of the EGF receptor and downstream signaling, with RalA and the exocyst likely controlling the secretion of the activating EGFR ligand and/or regulating EGFR endocytic pathway. In summary, we established RalA GTPase and the exocyst as a novel regulators of wrapping glia development providing a new perspective of the molecular pathways governing glia growth and development in the peripheral nervous system. With this, we expect to contribute for the identification of potential new points of intervention for potential improvement or development of novel therapies to mitigate symptoms caused by neurological disorders in which axonal ensheathment and/or Ral GTPase pathway are impaired. |
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| Autores principais: | Rodrigues, Joana Filipa da Silva |
| Assunto: | RalA GTPase Exocyst complex wrapping glia axonal ensheathment EGFR Drosophila |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Abstract The complexity of the nervous system demands and relies on a diversity of molecular processes essential for its correct development and functioning. Coordinated growth and communication between neurons and glia is crucial and indispensable for the physiological functions of the nervous system. Balanced neuronal and glial interaction and communication is decisive, for instance, to ensure suitable axonal insulation and fasciculation. Axonal ensheathment and insulation are critical for fast and reliable impulse conduction and disturbances in these processes often result in highly debilitating disorders, such as multiple sclerosis. Despite the obvious importance, our knowledge regarding the molecular players responsible for controlling the development, growth and communication between neurons and glia is still somewhat limited. In my thesis, we identified RalA GTPase and the exocyst complex as key regulators of axonal ensheathment in Drosophila melanogaster larval peripheral nerves. Detailed genetic analysis showed that RalA is required for wrapping glia growth and development, acting together with its effector exocyst. Our data suggests that this mechanism is regulated through the activation of the EGF receptor and downstream signaling, with RalA and the exocyst likely controlling the secretion of the activating EGFR ligand and/or regulating EGFR endocytic pathway. In summary, we established RalA GTPase and the exocyst as a novel regulators of wrapping glia development providing a new perspective of the molecular pathways governing glia growth and development in the peripheral nervous system. With this, we expect to contribute for the identification of potential new points of intervention for potential improvement or development of novel therapies to mitigate symptoms caused by neurological disorders in which axonal ensheathment and/or Ral GTPase pathway are impaired. |
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