Publikationsserver der Universitätsbibliothek Marburg

Titel:Untersuchungen zur Interaktion zwischen dem Kaliumkanal TREK-1 und Hämoxygenasen
Autor:Kocher , Vivien-Isabell (geb. Lauer)
Weitere Beteiligte: Preisig-Müller, Regina (PD Dr.)
Veröffentlicht:2012
URI:https://archiv.ub.uni-marburg.de/diss/z2012/0840
DOI: https://doi.org/10.17192/z2012.0840
URN: urn:nbn:de:hebis:04-z2012-08406
DDC: Medizin
Titel (trans.):Analyses of interaction between the potassium channel TREK-1 and hemeoxygenases
Publikationsdatum:2012-08-29
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Hämoxgenase, TEVC, potassium channel TREK-1 hemeoxygenase Yeast-two hybrid TEVC, TREK-1, Hefe-zwei-Hybrid-System, Kaliumkanal

Zusammenfassung:
Einleitung Der mechanosensitive K2P-Kanal TREK-1 ist stark in neuronalem Gewebe exprimiert und wird durch verschiedene chemische und physikalische Stimuli und einige Interaktionspartner reguliert. Verschiedene Studien haben gezeigt, dass TREK-1 an pathophysiologischen Prozessen wie Neuroprotektion, Schmerz und Depression beteiligt ist. TREK-1-Kanäle können das Ruhemembranpotential von Neuronen stabilisieren und spielen damit eine wichtige Rolle bei der Regulation der Membranerregbarkeit. Ziel dieser Arbeit war es, die direkte Interaktion der induzierbaren HO-1 und der konstitutiv exprimierten HO-2 mit TREK-1 zu vergleichen und Aminosäureregionen zu identifizieren, die für die Interaktion wichtig sind. Material und Methoden Um die direkte Interaktion von TREK-1 mit HO-1 und HO-2 zu testen, wurde das Split-Ubiquitin Hefe Zwei-Hybrid-System zur Untersuchung von Membran-proteinen verwendet. Dieses System nutzt die funktionelle Zusammenlagerung der beiden separierbaren Domänen des Ubiquitins, um Proteininteraktionen zu untersuchen. Die C-terminale Hälfte des Ubiquitins (Cub), an das ein artifizieller Transkriptionsfaktorkomplex gebunden ist, wurde an TREK-1 (Bait) fusioniert und die N-terminale Hälfte des Ubiquitins (NubG) wurde an HO-1 und HO-2 (Prey) fusioniert. Die Interaktion zwischen den Bait und Prey Proteinen bringt beide Ubiquitinhälften Cub und NubG zusammen, wodurch der Transkriptionsfaktorkomplex freigesetzt wird, in den Zellkern transloziert und dort die Expression von Reportergenen aktiviert. Die Hefezellen sind dann befähigt auf einem histidinfreien Selektionsmedium zu wachsen und beim -Galaktosidase-Assay eine Blaufärbung zu ergeben. Um die physiologische Relevanz der Interaktion von TREK-1 mit HO-1 und HO-2 zu untersuchen, wurden das Kanalprotein und die beiden Hämoxy-genasen in Xenopus laevis Oozyten coexprimiert und die TREK-1-Ströme mit Hilfe der Zwei-Elektroden-Spannungsklemme gemessen. Zur Herstellung von TREK-1-Konstrukten, die spezifische antigene Epitope enthalten, wurden das HA-Epitop (N-terminal) und das EGFP (C-terminal) mit Material and Methods To characterize the direct interaction of TREK-1 with HO-1 und HO-2, the split-ubiquitin yeast two-hybrid system was used, which is specialized for membrane proteins. This method utilizes complementation between separable domains of ubiquitin to study protein interactions. The C-terminal half of ubiquitin (Cub), along with an artificial transcription factor complex was fused to TREK-1 (bait) and the N-terminal half of ubiquitin (NubG) was fused to HO-1 or HO-2 (preys). Interaction between bait and prey proteins brings Cub and NubG together which activates the transcription factor complex. This complex enters the nucleus and activates the expression of several reporter genes which in turn enable the yeast cells to grow on a selective medium lacking histidine and turn blue in a -galactosidase assay. To investigate the physiological relevance of the interaction of TREK-1 with HO-1 and HO-2 the channel and the two heme oxygenase isoforms were co-expressed in Xenopus laevis oocytes and the TREK-1 currents were measured with the two-electrode voltage-clamp method. In order to produce TREK-1 constructs with specific antigenic epitopes the HA-epitope (N-terminally) and the EGFP (C-terminally) were fused to the TREK-1

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