0000000000725166

AUTHOR

Steffen Fricke

showing 3 related works from this author

Biallelic gephyrin variants lead to impaired GABAergic inhibition in a patient with developmental and epileptic encephalopathy

2021

Abstract Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition is linked to epilepsy. Gephyrin (Geph) is the principal scaffolding protein at inhibitory synapses and is essential for postsynaptic clustering of glycine (GlyRs) and GABA type A receptors. Consequently, gephyrin is crucial for maintaining the relationship between excitation and inhibition in normal brain function and mutations in the gephyrin gene (GPHN) are associated with neurodevelopmental disorders and epilepsy. We identified bi-allelic variants in the GPHN gene, namely the missense mutation c.1264G > A and splice acceptor variant c.1315-2A > G, in a patient wi…

Scaffold proteinBiologyInhibitory postsynaptic potentialEpilepsyPostsynaptic potentialGeneticsmedicineHumansMissense mutationReceptorBiologyMolecular BiologyGenetics (clinical)Brain DiseasesEpilepsyGephyrinMembrane ProteinsGeneral MedicineReceptors GABA-Amedicine.diseaseCell biologyChemistrySynapsesbiology.proteinHuman medicineReceptor clusteringCarrier ProteinsHuman Molecular Genetics
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Fast Regulation of GABAAR Diffusion Dynamics by Nogo-A Signaling.

2019

Summary: Precisely controlling the excitatory and inhibitory balance is crucial for the stability and information-processing ability of neuronal networks. However, the molecular mechanisms maintaining this balance during ongoing sensory experiences are largely unclear. We show that Nogo-A signaling reciprocally regulates excitatory and inhibitory transmission. Loss of function for Nogo-A signaling through S1PR2 rapidly increases GABAAR diffusion, thereby decreasing their number at synaptic sites and the amplitude of GABAergic mIPSCs at CA3 hippocampal neurons. This increase in GABAAR diffusion rate is correlated with an increase in Ca2+ influx and requires the calcineurin-mediated dephospho…

0301 basic medicineHippocampal formationInhibitory postsynaptic potentialGeneral Biochemistry Genetics and Molecular BiologyArticleSynaptic plasticityDephosphorylation03 medical and health sciences0302 clinical medicineSingle Particle Trackingmental disordersEi BalanceVeröffentlichung der TU Braunschweiglcsh:QH301-705.5Loss functionExcitationS1pr2S1PR2ddc:5InhibitionChemistryQuantum dotsCalcineurinGabaarsNogo-A; S1PR2 ; EI balance ; calcineurin ; inhibition ; excitation ; quantum dots ; GABAARs ; synaptic plasticity ; single particle trackingddc:57030104 developmental biologylcsh:Biology (General)Synaptic plasticityExcitatory postsynaptic potentialGABAergicNogo-ANeurosciencepsychological phenomena and processes030217 neurology & neurosurgery
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A new triple fluorescence reporter system for discrimination of Apobec1 and Apobec3 C-to-U RNA editing activities and editing-dependent protein expre…

2021

AbstractThe human body is composed of many different cell types which communicate with each other. In particular, the brain consists of billions of neurons and non-neuronal cells which are interconnected and require tight and precise regulation of cellular processes. RNA editing is a cellular process that diversifies gene function by enzymatic deamination of cytidine or adenine. This can result in changes of protein structure and function. Altered RNA editing is becoming increasingly associated with all kind of disease, but most approaches use advanced sequencing technologies to analyze bulk material. However, it is also becoming progressively evident that changes in RNA editing have to be …

Cell typeAPOBEC1RNACytidineBiologyCell biologychemistry.chemical_compoundmedicine.anatomical_structurechemistryRNA editingmedicineNeuronGeneFunction (biology)
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