Cyclin-dependent kinase 5 is involved in the phosphorylation of gephyrin and clustering of GABAA receptors at inhibitory synapses of hippocampal neurons

CDK5 has been implicated in neural functions including growth, neuronal migration, synaptic transmission and plasticity of excitatory chemical synapses. Here we report robust effects of CDK5 on phosphorylation of the postsynaptic scaffold protein gephyrin and clustering of inhibitory GABAA receptors...

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Bibliographic Details
Published in:PloS one 2014-08, Vol.9 (8), p.e104256
Main Authors: Kalbouneh, Heba, Schlicksupp, Andrea, Kirsch, Joachim, Kuhse, Jochen
Format: Article
Language:English
Subjects:
Animals
Biology
Biology and Life Sciences
Carrier Proteins - metabolism
Cell migration
Cells, Cultured
Cloning
Clustering
Clusters
Cyclin-dependent kinase
Cyclin-dependent kinase 5
Cyclin-Dependent Kinase 5 - genetics
Cyclin-Dependent Kinase 5 - metabolism
Engineering and Technology
Gene Expression
Gene Knockdown Techniques
Gephyrin
Hippocampus
Kinases
Localization
Membrane Proteins - metabolism
Migration
Mutagenesis
Neurons
Neuroplasticity
Pharmacology
Phosphorylation
Plasticity (neural)
Protein Binding
Protein Phosphatase 1 - metabolism
Protein Phosphatase 2 - metabolism
Protein Subunits
Proteins
Pyramidal Cells - metabolism
Rats
Receptor density
Receptors
Receptors, GABA-A - chemistry
Receptors, GABA-A - metabolism
Rodents
Site-directed mutagenesis
Synapses
Synapses - metabolism
Synaptic plasticity
Synaptic transmission
γ-Aminobutyric acid A receptors
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Summary:CDK5 has been implicated in neural functions including growth, neuronal migration, synaptic transmission and plasticity of excitatory chemical synapses. Here we report robust effects of CDK5 on phosphorylation of the postsynaptic scaffold protein gephyrin and clustering of inhibitory GABAA receptors in hippocampal neurons. shRNA-mediated knockdown of CDK5 and pharmacological inhibition of cyclin-dependent kinases reduced phosphorylated gephyrin clusters and postsynaptic γ2-containing GABAA receptors. Phosphorylation of S270 is antagonized by PP1/PP2a phosphatase and site-directed mutagenesis and in vitro phosphorylation experiments indicate that S270 is a putative CDK5 phosphorylation site of gephyrin. Our data suggest that CDK5 plays an essential role for the stability of gephyrin-dependent GABAA receptor clusters in hippocampal neurons.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0104256