<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Molecular mechanisms of neuronal structural maintenance and plasticity"^^ . "Dendrites receive and process synaptic inputs and thereby coordinate the connections and wiring \r\nbetween neurons which is essential for appropriate brain function. Dendritic structural plasticity is \r\nessential throughout development, however in adulthood, dendrites are stabilized and maintained \r\nto survive for years, if not throughout a neuron’s lifetime, to preserve optimal brain circuitry and \r\ncognitive function. Nevertheless, a degree of structural plasticity remains within mature neurons, \r\nallowing adaptation to diverse stimuli and experiences. Imbalances in the equilibrium between \r\nstructural plasticity and stability, such as atrophy or maladaptive plasticity, have been implicated in \r\nvarious neurological disorders. Despite the significance of this delicate balance, the understanding of \r\nmolecular and cellular mechanisms governing it remains limited. Vascular Endothelial Growth Factor \r\nD (VEGFD) is a crucial factor in preserving dendrite morphology of mature neurons. However, its \r\nparticipation in the context of structural plasticity remains uninvestigated. Moreover, its \r\ndownstream signaling pathways and how they affect the neuronal cytoskeleton to preserve \r\ndendrites is unknown.\r\nThis thesis shows that VEGFD expression is low in developing or adult neurons during activity-induced structural plasticity to allow morphological changes of dendrites. Employing time-lapse \r\nimaging coupled with machine-learning tracking of dendrites, I demonstrated that VEGFD achieves \r\nthis by maintaining the existing morphological state of neurons, through limiting dendrite elongation \r\nand destabilizing newly formed dendrites. Furthermore, I characterized the functions of ezrin and c-Raf in dendrite morphology, two cytoskeleton-related proteins identified as potential downstream \r\ntargets of VEGFD signaling through phospho-proteomic screening. Using both pharmacological and \r\ngenetic tools, I demonstrated that VEGFD causes the dephosphorylation of ezrin at tyrosine 478 via \r\nactivation of the striatal-enriched protein tyrosine phosphatase (STEP). Further, I showed through \r\noverexpression of a phospho-mutant ezrin that ezrin is a mediator of the VEGFD-induced \r\npreservation of dendrite structure during structural plasticity. Additionally, immunoprecipitation of \r\nVEGFD's receptor followed by mass spectrometry revealed the splicing regulator neuro-oncological \r\nventral antigen 2 (nova2) as a potential candidate protein in VEGFD signaling, offering a new path for \r\nfuture research. \r\nOverall, this work identified the downstream molecular and cellular processes of VEGFD signaling in \r\nplasticity and proposes that VEGFD regulates the balance between neuronal structural maintenance \r\nand plasticity by suppressing morphological alterations in dendrites."^^ . "2025" . . . . . . . "Bahar"^^ . "Aksan"^^ . "Bahar Aksan"^^ . . . . . . "Molecular mechanisms of neuronal structural maintenance and plasticity (Other)"^^ . . . . . . "Molecular mechanisms of neuronal structural maintenance and plasticity (Other)"^^ . . . . . . "Molecular mechanisms of neuronal structural maintenance and plasticity (Other)"^^ . . . . . . "Molecular mechanisms of neuronal structural maintenance and plasticity (Other)"^^ . . . . . . "Molecular mechanisms of neuronal structural maintenance and plasticity (Other)"^^ . . . . . . "Molecular mechanisms of neuronal structural maintenance and plasticity (PDF)"^^ . . "HTML Summary of #34907 \n\nMolecular mechanisms of neuronal structural maintenance and plasticity\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .