Die Funktionelle Rolle der Palmitilierung des 5-HT 1A Rezeptor

Papoucheva, Ekaterina

dc.contributor.advisor	Ponimaskin, Evgeni Prof. Dr.	de
dc.contributor.author	Papoucheva, Ekaterina	de
dc.date.accessioned	2012-04-16T14:46:08Z	de
dc.date.available	2013-01-30T23:50:46Z	de
dc.date.issued	2005-04-08	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0006-ABCA-5	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-64
dc.description.abstract	In dieser Studie wurde demonstriert, dass der 5-HT (1A) Rezeptor durch tioester-type Bindung palmitoyliert ist. Die Palmitoylierung wird nicht durch die Stimulation mit den Agonisten moduliert. Durch die Proteinsynthese Blockierung wurde gezeigt dass die Palmitilierung abhängig von der Proteinsynthese ist . Die pulse-chase Experimente demonstrieren dass die Rezeptormodifikation Stabil ist. Die zwei konservierten Cysteine 417 und 420 im C-terminal des Rezeptor wurden als potentiale Palmitoylierungsstellen identifiziert. Dies wurde durch die ortspezifische Mutagenese nachgewiesen. Die Funktionale Analyse von acylierungsdeffizienten Mutanten hat eine kritische Rolle der C-terminal Palmitoylierung für die Rezeptor- G-protein-kopplung und die Receptor-spezifischen Signale wie cAMP Synthese Inhibierung und die Erk1/2 Stimulation gezeigt.	de
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://webdoc.sub.gwdg.de/diss/copyr_diss.html	de
dc.title	Die Funktionelle Rolle der Palmitilierung des 5-HT 1A Rezeptor	de
dc.type	doctoralThesis	de
dc.title.translated	The Functional Role of Palmitoylation of the 5-HT 1A receptor	de
dc.contributor.referee	Richter, Diethelm Prof. Dr.	de
dc.date.examination	2004-11-03	de
dc.subject.dnb	570 Biowissenschaften, Biologie	de
dc.description.abstracteng	In the present study, we verified that the mouse 5-hydroxytryptamine(1A) (5-HT(1A)) receptor is modified by palmitic acid, which is covalently attached to the protein through a thioester-type bond. Palmitoylation efficiency was not modulated by receptor stimulation with agonists. Block of protein synthesis by cycloheximide resulted in a significant reduction of receptor acylation, suggesting that palmitoylation occurs early after synthesis of the 5-HT(1A) receptor. Furthermore, pulse-chase experiments demonstrated that fatty acids are stably attached to the receptor. Two conserved cysteine residues 417 and 420 located in the proximal C-terminal domain were identified as acylation sites by site-directed mutagenesis. To address the functional role of 5-HT(1A) receptor acylation, we have analyzed the ability of acylation-deficient mutants to interact with heterotrimeric G(i) protein and to modulate downstream effectors. Replacement of individual cysteine residues (417 or 420) resulted in a significantly reduced coupling of receptor with G(i) protein and impaired inhibition of adenylyl cyclase activity. When both palmitoylated cysteines were replaced, the communication of receptors with G alpha(i) subunits was completely abolished. Moreover, non-palmitoylated mutants were no longer able to inhibit forskolin-stimulated cAMP formation, indicating that palmitoylation of the 5-HT(1A) receptor is critical for the enabling of G(i) protein coupling/effector signaling. The receptor-dependent activation of extracellular signal-regulated kinase was also affected by acylation-deficient mutants, suggesting the importance of receptor palmitoylation for the signaling through the G beta gamma-mediated pathway, in addition to the G alpha(i)-mediated signaling.	de
dc.contributor.coReferee	Jahn, Reinhard Prof. Dr.	de
dc.contributor.thirdReferee	Schürmann, Friedrich-Wilhelm Prof. Dr.	de
dc.subject.topic	Mathematics and Computer Science	de
dc.subject.ger	G-proteine-gekoppelte Rezeptor	de
dc.subject.ger	Palmitoylierung	de
dc.subject.ger	Serotonin	de
dc.subject.eng	G-protein-coupled receptor	de
dc.subject.eng	palmitoylation	de
dc.subject.eng	serotonin	de
dc.subject.bk	42.15	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-102-2	de
dc.identifier.purl	webdoc-102	de
dc.affiliation.institute	Biologische Fakultät inkl. Psychologie	de
dc.subject.gokfull	WH	de
dc.subject.gokfull	WF	de
dc.identifier.ppn	487798775	de

Dateien

Name:papoucheva.pdf

Größe:1.324Mb

Format:PDF

Beschreibung:Dissertation

Öffnen

Name:: papoucheva.pdf
Größe:: 1.324Mb
Format:: PDF
Beschreibung:: Dissertation

Öffnen

Das Dokument erscheint in:

Fakultät für Biologie und Psychologie (inkl. GAUSS) [1621]

Zur Kurzanzeige