A5003007188- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Pregnancy and preeclampsia studies
- Cellular transport and secretion
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Neuroendocrine regulation and behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Gout, Hyperuricemia, Uric Acid
- Gestational Diabetes Research and Management
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Lipid Membrane Structure and Behavior
- Photochromic and Fluorescence Chemistry
- Neurotransmitter Receptor Influence on Behavior
- Dental materials and restorations
- Birth, Development, and Health
- Herpesvirus Infections and Treatments
- Metabolism and Genetic Disorders
- Virus-based gene therapy research
- Photoreceptor and optogenetics research
Pennsylvania State University
2014-2024
University Hospital of Bern
2013-2022
University of Bern
2011-2022
National Institutes of Health
2014-2022
National Institute of Dental and Craniofacial Research
2019-2022
University of Regensburg
2019
University of California, Los Angeles
2019
University College London
2019
Universitätsklinik für Frauenheilkunde und Geburtshilfe
2018
Park University
2017
Human AP-2 is a sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to stimulate transcription of selected genes. Here, we report the isolation characterization human cDNA clone containing entire protein-coding region AP-2. The deduced primary amino acid sequence does not contain domain resembling any previously identified DNA binding motif. However, an interesting feature clustered arrangement proline glutamine residues have been found...
Vigilance, anxiety, epileptic activity, and muscle tone can be modulated by drugs acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABAA) receptors. In vivo, BZ sites are potential targets for endogenous ligands regulating corresponding central nervous system states. To assess physiological relevance sites, mice were generated containing GABAA receptors devoid sites. Following targeted disruption gamma 2 subunit gene, 94% absent in brain neonatal mice, while number...
After increasing the width of attached gingiva by free palatal mucosa transplants, 20 procedures with coronal flap repositioning were performed on 41 teeth gingival recessions in 13 young adults. The amount recession and clinical sulcus depth measured pre-operatively 1, 6 12 months after surgery; osseous dehiscence was during surgery. No significant differences found among reduction values reattachment post-operatively. Although a correlation between degree preoperatively 1 month...
Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes GABAA receptor mutant mice can be reversed treatment conventional antidepressants drugs, as well subanesthetic doses ketamine. Thus GABAergic deficits may causally contribute to disorders, while therapies enhance synaptic transmission. Here we tested the hypothesis sustained enhancement transmission alone...
Enhancer binding protein AP-4 is a transcription factor that activates both viral and cellular genes by to the symmetrical DNA sequence, CAGCTG. Here, we report molecular cloning characterization of human cDNAs. The deduced amino acid sequence reveals helix-loop-helix (HLH) protein. Like other members this family, HLH motif adjacent basic domain are necessary sufficient confer site-specific binding. However, unlike proteins, also contains two additional dimerization motifs consisting leucine...
The expression of the transcription factor AP-2 recently has been shown to be enhanced during retinoic acid (RA)-induced differentiation NT2 cells, a human teratocarcinoma cell line. Here we show that this induction mRNA is at level and transient, reaching peak 48-72 hr after addition RA declining thereafter, even in continuous presence RA. Increased levels are reflected similar elevation protein accompanied by an increase AP-2-binding site-dependent transcriptional activity reporter gene....
Glycine receptors (GlyRs) and specific subtypes of GABA A are clustered at synapses by the multidomain protein gephyrin, which in turn is translocated to cell membrane GDP-GTP exchange factor collybistin. We report characterization several new variants collybistin, created alternative splicing exons encoding an N-terminal src homology 3 (SH3) domain three alternate C termini (CB1, CB2, CB3). The presence SH3 negatively regulates ability collybistin translocate gephyrin submembrane...
The neurotransmitter GABA activates heteropentameric A receptors, which are composed mostly of α, β, and γ2 subunits. Regulated membrane trafficking subcellular targeting receptors is important for determining the efficacy GABAergic inhibitory function. Of special interest subunit, dispensable assembly insertion functional but essential accumulation at synapses. In a search novel receptor proteins, we have used SOS-recruitment system isolated Golgi-specific DHHC zinc finger protein (GODZ) as...
Stressful experiences in early life are known risk factors for anxiety and depressive illnesses, they inhibit hippocampal neurogenesis the expression of GABA A receptors adulthood. Conversely, deficits GABAergic neurotransmission reduced implicated etiology pathological diverse mood disorders. Mice that heterozygous γ2 subunit exhibit a modest functional deficit mainly postsynaptic is associated with behavioral, cognitive, pharmacological phenotype indicative heightened trait anxiety. Here...
Golgi-specific DHHC (Asp-His-His-Cys) zinc finger protein (GODZ) is a family palmitoyl acyltransferase that implicated in palmitoylation and regulated trafficking of diverse substrates function either at inhibitory or excitatory synapses. Of particular interest the γ2 subunit GABA A receptors, which required for targeting these receptors to Here, we report GODZ and, lesser extent, its close paralog sertoli cell gene with domain-β (SERZ-β) are main members enzymes able palmitoylate...
Major depressive disorder is increasingly recognized to involve functional deficits in both gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission. To elucidate the relationship between these phenotypes, we used GABAA receptor γ2 subunit heterozygous (γ2(+/-)) mice, which previously characterized as a model animal with construct, face, predictive validity for major disorder.To assess possible consequences of GABAergic on transmission, quantitated cell surface expression...
In rat hippocampal cultures, we show by multilabeling immunocytochemistry that pyramidal cells, which receive little or no GABAergic input, mistarget alpha2-GABA(A) receptors and gephyrin to glutamatergic terminals. This mismatch does not occur in neurons innervated numerous A similar phenomenon has been reported for isolated autaptic (Rao et al., 2000). synapses typically form multiple release sites apposed GABA(A) receptor clusters. Remarkably, dystrophin, a protein highly abundant...
Modulation of the concentration postsynaptic GABA A receptors contributes to functional plasticity inhibitory synapses. The γ2 subunit receptor is specifically required for clustering these receptors, recruitment submembrane scaffold protein gephyrin sites, and function GABAergic To elucidate this mechanism, we here have mapped domains restoration in mutant neurons. Transfection -/- neurons with but not α2 rescues results restores amplitude frequency miniature currents wild-type levels....
Clustering of inhibitory γ-aminobutyric acidA (GABAA) and glycine receptors at synapses is thought to involve key interactions between the receptors, a "scaffolding" protein known as gephyrin RhoGEF collybistin. We report identification balanced chromosomal translocation in female patient presenting with disturbed sleep-wake cycle, late-onset epileptic seizures, increased anxiety, aggressive behavior, mental retardation, but not hyperekplexia. Fine mapping breakpoint indicates disruption...
We have analyzed the expression of endogenous histone H4 genes and a newly introduced gene in 21-Tb cells, mouse mastocytoma cell-cycle mutant. Endogenous mRNAs were less abundant by factor 120-180 G1-arrested than exponentially multiplying cells. However, transcription rates only decreased 3 under these conditions, as determined vitro elongation nascent transcripts. This indicates that post-transcriptional control mRNA levels is important, accord with published data. gene, modified...