{"id":{"repo_id":"goettingen","oai_identifier":"oai:ediss.uni-goettingen.de:11858/00-1735-0000-0006-ABCA-5"},"canonical_url":"https://search.dev.ndltd.org/etd/goettingen/oai:ediss.uni-goettingen.de:11858/00-1735-0000-0006-ABCA-5","repository":{"repo_id":"goettingen","name":"Georg-August-Universität Göttingen","base_url":"https://ediss.uni-goettingen.de/oai/request"},"display":{"title":"Die Funktionelle Rolle der Palmitilierung des 5-HT 1A Rezeptor","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Papoucheva, Ekaterina"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Ponimaskin, Evgeni Prof. Dr.","Richter, Diethelm Prof. Dr.","Jahn, Reinhard Prof. Dr.","Schürmann, Friedrich-Wilhelm Prof. Dr."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-04-16T14:46:08Z","date_published":"2012-04-16T14:46:08Z","updated_at":"2026-07-24T02:24:11Z","subjects":["570 Biowissenschaften, Biologie","Biologie","G-proteine-gekoppelte Rezeptor","Palmitoylierung","Serotonin","G-protein-coupled receptor","palmitoylation","42.15","WH","WF"],"languages":["eng"],"rights":[],"rights_urls":["https://webdoc.sub.gwdg.de/diss/copyr_diss.html"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dx.doi.org/10.53846/goediss-64","urn:nbn:de:gbv:7-webdoc-102-2","webdoc-102","487798775"],"render_values":[{"text":"https://dx.doi.org/10.53846/goediss-64","href":"https://dx.doi.org/10.53846/goediss-64","code":true},{"text":"urn:nbn:de:gbv:7-webdoc-102-2","href":null,"code":true},{"text":"webdoc-102","href":null,"code":true},{"text":"487798775","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/11858/00-1735-0000-0006-ABCA-5","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Ponimaskin, Evgeni Prof. Dr.","Richter, Diethelm Prof. Dr.","Jahn, Reinhard Prof. Dr.","Schürmann, Friedrich-Wilhelm Prof. Dr."]},{"key":"dc:creator","label":"Author","values":["Papoucheva, Ekaterina"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-04-16T14:46:08Z","2013-01-30T23:50:46Z","2005-04-08","2004-11-03"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["570 Biowissenschaften, Biologie","Biologie","G-proteine-gekoppelte Rezeptor","Palmitoylierung","Serotonin","G-protein-coupled receptor","palmitoylation","42.15","WH","WF"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://webdoc.sub.gwdg.de/diss/copyr_diss.html"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/11858/00-1735-0000-0006-ABCA-5","https://dx.doi.org/10.53846/goediss-64","urn:nbn:de:gbv:7-webdoc-102-2","webdoc-102","487798775"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Die Funktionelle Rolle der Palmitilierung des 5-HT 1A Rezeptor","The Functional Role of Palmitoylation of the 5-HT 1A receptor"]}]}],"canonical_facts":{"dc:contributor":["Ponimaskin, Evgeni Prof. Dr.","Richter, Diethelm Prof. Dr.","Jahn, Reinhard Prof. Dr.","Schürmann, Friedrich-Wilhelm Prof. Dr."],"dc:creator":["Papoucheva, Ekaterina"],"dc:date":["2012-04-16T14:46:08Z","2013-01-30T23:50:46Z","2005-04-08","2004-11-03"],"dc:description":["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.","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."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/11858/00-1735-0000-0006-ABCA-5","https://dx.doi.org/10.53846/goediss-64","urn:nbn:de:gbv:7-webdoc-102-2","webdoc-102","487798775"],"dc:language":["eng"],"dc:rights":["https://webdoc.sub.gwdg.de/diss/copyr_diss.html"],"dc:subject":["570 Biowissenschaften, Biologie","Biologie","G-proteine-gekoppelte Rezeptor","Palmitoylierung","Serotonin","G-protein-coupled receptor","palmitoylation","42.15","WH","WF"],"dc:title":["Die Funktionelle Rolle der Palmitilierung des 5-HT 1A Rezeptor","The Functional Role of Palmitoylation of the 5-HT 1A receptor"],"dc:type":["doctoralThesis"]},"updated_at":"2026-07-24T02:24:11Z"}