Buchumschlag

Phosphorylation of gephyrin in hippocampalneurons by cyclin-dependent kinase CDK5 at Ser-270 is dependent on collybistin

Gephyrin is a scaffold protein essential for the postsynaptic clustering of inhibitory glycine and different subtypes of GABAA receptors. The cellular and molecular mechanisms involved in gephyrin-mediated receptor clustering are still not well understood. Here we provide evidence that the gephyrin-...

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Bibliographische Detailangaben
Hauptverfasser: Kuhse, Jochen (VerfasserIn) , Kalbouneh, Hebah (VerfasserIn) , Schlicksupp, Andrea (VerfasserIn) , Nawrotzki, Ralph (VerfasserIn) , Kirsch, Joachim (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 2012
In: The journal of biological chemistry
Year: 2012, Jahrgang: 287, Heft: 37, Pages: 30952-30966
ISSN:1083-351X
DOI:10.1074/jbc.M112.349597
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1074/jbc.M112.349597
Verlag, kostenfrei, Volltext: http://www.jbc.org/content/287/37/30952
Volltext
Verfasserangaben:Jochen Kuhse, Heba Kalbouneh, Andrea Schlicksupp, Susanne Mükusch, Ralph Nawrotzki, and Joachim Kirsch
Beschreibung
Zusammenfassung:Gephyrin is a scaffold protein essential for the postsynaptic clustering of inhibitory glycine and different subtypes of GABAA receptors. The cellular and molecular mechanisms involved in gephyrin-mediated receptor clustering are still not well understood. Here we provide evidence that the gephyrin-binding protein collybistin is involved in regulating the phosphorylation of gephyrin. We demonstrate that the widely used monoclonal antibody mAb7a is a phospho-specific antibody that allows the cellular and biochemical analysis of gephyrin phosphorylation at Ser-270. In addition, another neighbored epitope determinant was identified at position Thr-276. Analysis of the double mutant gephyrinT276A,S277A revealed significant reduction in gephyrin cluster formation and altered oligomerization behavior of gephyrin. Moreover, pharmacological inhibition of cyclin-dependent kinases in hippocampal neurons reduced postsynaptic gephyrin mAb7a immunoreactivities. In vitro phosphorylation assays and phosphopeptide competition experiments revealed a phosphorylation at Ser-270 depending on enzyme activities of cyclin-dependent kinases CDK1, -2, or -5. These data indicate that collybistin and cyclin-dependent kinases are involved in regulating the phosphorylation of gephyrin at postsynaptic membrane specializations.
Beschreibung:Gesehen am 22.11.2018
Beschreibung:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M112.349597

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