• Deutsch
    • English
  • English 
    • Deutsch
    • English
  • Login
Item View 
  •   Home
  • Naturwissenschaften, Mathematik und Informatik
  • Fakultät für Biologie und Psychologie (inkl. GAUSS)
  • Item View
  •   Home
  • Naturwissenschaften, Mathematik und Informatik
  • Fakultät für Biologie und Psychologie (inkl. GAUSS)
  • Item View
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

The Functional Role of Palmitoylation of the 5-HT 1A receptor

by Ekaterina Papoucheva
Doctoral thesis
Date of Examination:2004-11-03
Date of issue:2005-04-08
Advisor:Prof. Dr. Evgeni Ponimaskin
Referee:Prof. Dr. Diethelm Richter
Referee:Prof. Dr. Reinhard Jahn
Referee:Prof. Dr. Friedrich-Wilhelm Schürmann
crossref-logoPersistent Address: http://dx.doi.org/10.53846/goediss-64

 

 

Files in this item

Name:papoucheva.pdf
Size:1.32Mb
Format:PDF
Description:Dissertation
ViewOpen

The following license files are associated with this item:


Abstract

English

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.
Keywords: G-protein-coupled receptor; palmitoylation; serotonin

Other Languages

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.
Schlagwörter: G-proteine-gekoppelte Rezeptor; Palmitoylierung; Serotonin
 

Statistik

Publish here

Browse

All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesType

Help & Info

Publishing on eDissPDF GuideTerms of ContractFAQ

Contact Us | Impressum | Cookie Consents | Data Protection Information | Accessibility
eDiss Office - SUB Göttingen (Central Library)
Platz der Göttinger Sieben 1
Mo - Fr 10:00 – 12:00 h


Tel.: +49 (0)551 39-27809 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
ediss_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]
Göttingen State and University Library | Göttingen University
Medicine Library (Doctoral candidates of medicine only)
Robert-Koch-Str. 40
Mon – Fri 8:00 – 24:00 h
Sat - Sun 8:00 – 22:00 h
Holidays 10:00 – 20:00 h
Tel.: +49 551 39-8395 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
bbmed_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]