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Titel: The regulation of the expression of PMCA isoforms by neuroplastin has an impact on the calcium clearance in cultured hippocampal neurons
Autor(en): Junge, Lennart
Gutachter: Brunner-Weinzierl, Monika
Roßner, Steffen
Körperschaft: Otto-von-Guericke-Universität Magdeburg
Erscheinungsdatum: 2021
Art: Dissertation
Tag der Verteidigung: 2021
Sprache: Englisch
Herausgeber: Otto-von-Guericke-Universität Magdeburg
URN: urn:nbn:de:gbv:ma9:1-1981185920-412629
Schlagwörter: Hirnfunktion
Nervenzelle
Calciumstoffwechsel
Zusammenfassung: The restoration of basal cytosolic calcium levels after excitation is essential for neurons. An important part of the machinery responsible for calcium clearance is the Plasma Membrane ATPAse (PMCA), which pumps calcium ions from the cytosol to the extracellular space with high affinity. Four PMCA paralogs are specific for distinct cell types and functions. As suggested recently, PMCAs form complexes with neuroplastin (Np) and their expression levels are affected differently by this interaction. To test the hypothesis that the ability of neuroplastin to stimulate PMCA surface expression and to increase the speed of the calcium clearance depends on the neuroplastin interaction partner TRAF6, the PMCAs were overexpressed together with neuroplastin in cell lines and neurons. The experiments showed that in COS-7 cells the overexpression of neuroplastin increased the protein level of the neuron-specific PMCA2 more than of the other PMCAs. Since neuroplastin and all PMCAs have a binding site for the signal adapter TRAF6, I tested if this protein might be relevant for their interaction. By employing a neuroplastin mutant construct missing the TRAF6 binding site I could show, that the increase of PMCA2 expression levels caused by neuroplastin in HEK cells and hippocampal neurons is TRAF6-independent. Against our expectation, in calcium imaging experiments I could show that increased PMCA levels due to overexpression of neuroplastin lead to slowing down calcium extrusion after stimulation, indicating that the influence of neuroplastin on the calcium balance is more complex. Additional factors such as the time and duration of the transfection need to be considered in order to understand the influence of the interaction of PMCA and neuroplastin on the calcium balance.
URI: https://opendata.uni-halle.de//handle/1981185920/41262
http://dx.doi.org/10.25673/39308
Open-Access: Open-Access-Publikation
Nutzungslizenz: (CC BY-SA 4.0) Creative Commons Namensnennung - Weitergabe unter gleichen Bedingungen 4.0 International(CC BY-SA 4.0) Creative Commons Namensnennung - Weitergabe unter gleichen Bedingungen 4.0 International
Enthalten in den Sammlungen:Medizinische Fakultät

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