Manzke, Till U.

[["dc.bibliographiccitation.artnumber","28"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.lastpage","7"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Manzke, Till"],["dc.date.accessioned","2019-07-09T11:45:09Z"],["dc.date.available","2019-07-09T11:45:09Z"],["dc.date.issued","2018"],["dc.description.abstract","Mutations in the transcription factor methyl-CpG-binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome (RTT). Besides many other neurological problems, RTT patients show irregular breathing with recurrent apneas or breath-holdings. MeCP2-deficient mice, which recapitulate this breathing phenotype, show a dysregulated, persistent expression of G-protein-coupled serotonin receptor 5-ht5b (Htr5b) in the brainstem. To investigate whether the persistence of 5-ht5b expression is contributing to the respiratory phenotype, we crossbred MeCP2-deficient mice with 5-ht5b-deficient mice to generate double knockout mice (Mecp2-/y ;Htr5b-/-). To compare respiration between wild type (WT), Mecp2-/y and Mecp2-/y ;Htr5b-/- mice, we used unrestrained whole-body plethysmography. While the breathing of MeCP2-deficient male mice (Mecp2-/y ) at postnatal day 40 is characterized by a slow breathing rate and the occurrence of prolonged respiratory pauses, we found that in MeCP2-deficient mice, which also lacked the 5-ht5b receptor, the breathing rate and the number of pauses were indistinguishable from WT mice. To test for a potential mechanism, we also analyzed if the known coupling of 5-ht5b receptors to Gi proteins is altering second messenger signaling. Tissue cAMP levels in the medulla of Mecp2-/y mice were decreased as compared to WT mice. In contrast, cAMP levels in Mecp2-/y ;Htr5b-/- mice were indistinguishable from WT mice. Taken together, our data points towards a role of 5-ht5b receptors within the complex breathing phenotype of MeCP2-deficient mice."],["dc.identifier.doi","10.3389/fnmol.2018.00028"],["dc.identifier.pmid","29515365"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15043"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59167"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Persistent Expression of Serotonin Receptor 5b Alters Breathing Behavior in Male MeCP2 Knockout Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","299"],["dc.bibliographiccitation.journal","Frontiers in molecular neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Niebert, Sabine"],["dc.contributor.author","van Belle, Gijsbert J."],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Niebert, Marcus"],["dc.date.accessioned","2019-07-09T11:44:34Z"],["dc.date.available","2019-07-09T11:44:34Z"],["dc.date.issued","2017"],["dc.description.abstract","Previously, we described the dysregulation of serotonin (5-HT) receptor subtype 5b (5-ht5b) in a mouse model of Rett syndrome (RTT). 5-ht5b has not been extensively studied, so we set out to characterize it in more detail. Unlike common cell surface receptors, 5-ht5b displays no membrane expression, while receptor clusters are located in endosomes. This unusual subcellular localization is at least in part controlled by glycosylation of the N-terminus, with 5-ht5b possessing fewer glycosylation sites than related receptors. We analyzed whether the localization to endosomes has any functional relevance and found that 5-ht5b receptors can specifically interact with 5-HT1A receptors and retain them in endosomal compartments. This interaction reduces 5-HT1A surface expression and is mediated by interactions between the fourth and fifth trans-membrane domain (TMD). This possibly represents a mechanism by which 5-ht5b receptors regulate the activity of other 5-HT receptor."],["dc.identifier.doi","10.3389/fnmol.2017.00299"],["dc.identifier.pmid","28983239"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59037"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The Serotonin Receptor Subtype 5b Specifically Interacts with Serotonin Receptor Subtype 1A."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]