Effects of distinct collybistin isoforms on the formation of GABAergic synapses in hippocampal neurons

Körber, Christoph; Richter, Andréa; Kaiser, Michaela; Schlicksupp, Andrea; Mükusch, Susanne; Kuner, Thomas; Kirsch, Joachim; Kuhse, Jochen

doi:10.1016/j.mcn.2012.05.006

Cited by 26 publications

(21 citation statements)

References 32 publications

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“…Immunoblot Analysis-Western blotting as described in Körber et al (30). Membranes were probed with mouse monoclonal mAb7a antibody (1:200), rabbit anti-gephyrin antibody Ab-175 (1:200) (32), and anti-myc antibody (1:200, Santa Cruz, catalog no.…”

Section: Construction Of Expression Plasmids and Knockdown Vectors-mentioning

confidence: 99%

“…mAb7a antibody was preincubated with peptides with concentrations from 2 to 0.25 mg/ml in 50 l of TBSTween (30) with a 1:20 dilution of mAb7a for 1 h at room temperature. After a centrifugation step (13,200 rpm, 15 min), the preincubated mAb7a/peptide solution was further diluted 10-fold with blocking solution (30) and applied to immunoblots using PVDF membrane stripes. The further procedure was as described above for immunoblots.…”

Section: Construction Of Expression Plasmids and Knockdown Vectors-mentioning

confidence: 99%

“…Thus, reduction of Cb expression in hippocampal neurons reduced the staining of gephyrin clusters with mAb7a specifically (for a more detailed functional analysis of Cb knockdown experiments, see Ref. 30).…”

Section: Cb Knockdown Abolishes the Formation Of Gephyrin Clusters Inmentioning

confidence: 99%

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Phosphorylation of Gephyrin in Hippocampal Neurons by Cyclin-dependent Kinase CDK5 at Ser-270 Is Dependent on Collybistin

Kuhse

Kalbouneh

Schlicksupp

et al. 2012

Journal of Biological Chemistry

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Background: Formation of inhibitory synapses in the CNS is dependent on cluster formation of the scaffold protein gephyrin. Results: Knockdown of collybistin and inhibition of cyclin-dependent kinases (CDK1,-2, and -5) abolished the phosphorylation of gephyrin detected by mAb7a at Ser-270. Conclusion: Gephyrin detected with mAb7a is phosphorylated at Ser-270. Significance: These data suggest a novel view on kinases involved in gephyrin phosphorylation.

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Section: Construction Of Expression Plasmids and Knockdown Vectors-mentioning

confidence: 99%

Section: Construction Of Expression Plasmids and Knockdown Vectors-mentioning

confidence: 99%

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Phosphorylation of Gephyrin in Hippocampal Neurons by Cyclin-dependent Kinase CDK5 at Ser-270 Is Dependent on Collybistin

Kuhse

Kalbouneh

Schlicksupp

et al. 2012

Journal of Biological Chemistry

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“…37,73 Importantly, the coexpression of collybistin II and gephyrin in non-neuronal cells was shown to induce submembranous collybistin/gephyrin microaggregates that also accumulated hetero-oligomeric GlyRs. 72 However, CB2 SH3+ is inactive in dendritic gephyrin clustering, indicating that the alternative splicing of collybistin has functional importance in the development of inhibitory synapse (Harvey et al; 37 also Tyagarajan et al and Korber et al 39,75 ) for the involvement of Cdc42 in regulating the clustering of gephyrin). Mutation of glycine 55 to alanine (G55A) in the SH3 domain of collybistin has been linked to hyperekplexia and epilepsy, reinforcing the importance of this domain of collybistin in its dendritic trafficking and association with gephyrin.…”

Section: Collybistinmentioning

confidence: 99%

“…Strikingly, collybistin-deficient mice did not exhibit deficits in glycinergic synaptic transmission, suggesting that collybistin is dispensable for gephyrin-mediated GlyR clustering in glycinergic synapses, but is required for the gephyrinmediated clustering of certain GABA A receptors at inhibitory postsynaptic sites. 75,[82][83][84] Profilin and Mena A study seeking the linkage between gephyrin and microfilament identified profilin, Mena and G-actin as gephyrin-binding proteins. 85 Endogenous profilin and Mena were found to colocalize with gephyrin in the inhibitory synapses of spinal cord neurons, and were enriched in gephyrin-rich domains of the neuronal plasma membrane.…”

Section: Collybistinmentioning

confidence: 99%

Gephyrin: a central GABAergic synapse organizer

Choii

2015

Exp Mol Med

126

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Gephyrin is a central element that anchors, clusters and stabilizes glycine and γ-aminobutyric acid type A receptors at inhibitory synapses of the mammalian brain. It self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins. Intriguingly, the clustering of gephyrin, which is regulated by multiple posttranslational modifications, is critical for inhibitory synapse formation and function. In this review, we summarize the basic properties of gephyrin and describe recent findings regarding its roles in inhibitory synapse formation, function and plasticity. We will also discuss the implications for the pathophysiology of brain disorders and raise the remaining open questions in this field.

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The phenotypic spectrum of ARHGEF9 includes intellectual disability, focal epilepsy and febrile seizures

et al. 2017

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Mutations or structural genomic alterations of the X-chromosomal gene ARHGEF9 have been described in male and female patients with intellectual disability. Hyperekplexia and epilepsy were observed to a variable degree, but incompletely described. Here, we expand the phenotypic spectrum of ARHGEF9 by describing a large Ethiopian-Jewish family with epilepsy and intellectual disability. The four affected male siblings, their unaffected parents and two unaffected female siblings were recruited and phenotyped. Parametric linkage analysis was performed using SNP microarrays. Variants from exome sequencing in two affected individuals were confirmed by Sanger sequencing. All affected male siblings had febrile seizures from age 2-3 years and intellectual disability. Three developed afebrile seizures between age 7-17 years. Three showed focal seizure semiology. None had hyperekplexia. A novel ARHGEF9 variant (c.967G>A, p.G323R, NM_015185.2) was hemizygous in all affected male siblings and heterozygous in the mother. This family reveals that the phenotypic spectrum of ARHGEF9 is broader than commonly assumed and includes febrile seizures and focal epilepsy with intellectual disability in the absence of hyperekplexia or other clinically distinguishing features. Our findings suggest that pathogenic variants in ARHGEF9 may be more common than previously assumed in patients with intellectual disability and mild epilepsy.

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Effects of distinct collybistin isoforms on the formation of GABAergic synapses in hippocampal neurons

Cited by 26 publications

References 32 publications

Phosphorylation of Gephyrin in Hippocampal Neurons by Cyclin-dependent Kinase CDK5 at Ser-270 Is Dependent on Collybistin

Phosphorylation of Gephyrin in Hippocampal Neurons by Cyclin-dependent Kinase CDK5 at Ser-270 Is Dependent on Collybistin

Gephyrin: a central GABAergic synapse organizer

The phenotypic spectrum of ARHGEF9 includes intellectual disability, focal epilepsy and febrile seizures

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