A5077402047- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Cannabis and Cannabinoid Research
- Neuropeptides and Animal Physiology
- Biochemical Analysis and Sensing Techniques
- Pancreatic function and diabetes
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Neurotransmitter Receptor Influence on Behavior
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience of respiration and sleep
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Nerve injury and regeneration
- Thallium and Germanium Studies
- Pharmacogenetics and Drug Metabolism
- Immune Response and Inflammation
- Neurobiology and Insect Physiology Research
- RNA and protein synthesis mechanisms
- 14-3-3 protein interactions
- Hypothalamic control of reproductive hormones
- MicroRNA in disease regulation
Czech Academy of Sciences, Institute of Molecular Genetics
2008-2024
Czech Academy of Sciences
2004-2024
Centre National de la Recherche Scientifique
1998-2019
Inserm
2005-2019
Université de Montpellier
2005-2019
Charles University
2000-2019
Czech Academy of Sciences, Institute of Experimental Medicine
2002-2005
Institut de Génomique Fonctionnelle
2005
National Institutes of Health
1996-2003
University of Basel
2002
The membrane-associated guanylate kinases [Chapsyn-110/postsynaptic density-93 (PSD-93), synapse-associated protein-90 (SAP-90)/PSD-95, and SAP-102] are believed to cluster anchor NMDA receptors at the synapse play a role in signal transduction. We have investigated developmental changes expression of these proteins rat hippocampus using biochemical analyses quantitative immunogold electron microscopy. At postnatal day 2 (P2), SAP-102 was highly expressed, whereas PSD-93 PSD-95 were low....
Assembly of fully functional GABA(B) receptors requires heteromerization the GABA(B(1)) and GABA(B(2)) subunits. It is thought that undergo coiled-coil dimerization in their cytoplasmic C termini assembly necessary to overcome retention endoplasmatic reticulum (ER). We investigated mechanism underlying trafficking cell surface. identified a signal, RSRR, proximal domain when deleted or mutagenized allows for surface delivery absence GABA(B(2)). A similar motif, RXR, was recently shown...
Reelin is a secreted protein that regulates brain layer formation during embryonic development. binds several receptors, including two members of the low-density lipoprotein (LDL) receptor family, apolipoprotein E 2 (ApoER2) and very-low-density (VLDLR). Despite high level expression ApoER2 in postnatal brain, their functions adult CNS remain elusive. Here, using electrophysiological, immunocytochemical, biochemical approaches cultured hippocampal neurons, we show controls change subunit...
The recent discovery of positive allosteric modulators (PAMs) for G-protein-coupled receptors open new possibilities to control a number physiological and pathological processes. Understanding the mechanism action such compounds will provide information on activation process these important receptors. Within last 10 years, studies indicate that can form dimers, but functional significance this phenomenon remains elusive. Here we used metabotropic glutamate as model, because receptors, which...
Both subunits in the metabotropic glutamate receptor 1 dimer move relative to each other before one adopts an active conformation.
The γ-amino-<i>n</i>-butyric acid type B (GABA<sub>B</sub>) receptor is composed of two subunits, GABA<sub>B</sub>1 and GABA<sub>B</sub>2, belonging to the family 3 heptahelix receptors. These proteins possess domains, a seven transmembrane core an extracellular domain containing agonist binding site. This likely fold like bacterial periplasmic that are constituted lobes close upon ligand binding. Here, using molecular modeling site-directed mutagenesis, we have identified residues in...
The γ-aminobutyrate B (GABA<sub>B</sub>) receptor is the first discovered G-protein-coupled (GPCR) that needs two subunits, GB1 and GB2, to form a functional receptor. extracellular domain (ECD) binds GABA, GB2 contains enough molecular determinants for G-protein activation. precise role of subunits in coupling investigated. are structurally related metabotropic glutamate, Ca<sup>2+</sup>-sensing other family 3 GPCRs which second (i2) as well third (i3) intracellular loop play important...
Cell surface expression of transmembrane proteins is strictly regulated. Mutually exclusive interaction with COPI or 14-3-3 has been proposed as a mechanism underlying such trafficking control various proteins. In particular, dimers have to “sense” correctly assembled oligomers, allowing their targeting by preventing COPI-mediated intracellular retention. Here we examined whether involved in the quality heterodimeric G protein-coupled GABA B receptor. Its GB1 subunit, carrying retention...
Many diseases of the nervous system are accompanied by alterations in synaptic functions. Synaptic plasticity mediated endogenous cannabinoid involves activation receptor 1 (CB1R). The principles CB1R signaling must be understood detail for its therapeutic exploration. We detected Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein (SGIP1) as a novel partner. SGIP1 is functionally linked to clathrin-mediated endocytosis and overexpression animals leads...
We examined the regulation of mGlu2 and mGlu3 metabotropic glutamate receptor signaling prompted by emerging role these subtypes as therapeutic targets for psychiatric disorders, such anxiety schizophrenia. In transfected human embryonic kidney 293 cells, G-protein-coupled kinase (GRK) 2 GRK3 fully desensitized agonist-dependent inhibition cAMP formation mediated receptors. contrast, GRK2 or other GRKs did not desensitize response to activation. Desensitization receptors required an intact...
Background and Purpose Src homology 3‐domain growth factor receptor‐bound 2‐like endophilin interacting protein 1 (SGIP1) interacts with cannabinoid CB receptors. SGIP1 is abundantly principally expressed within the nervous system. receptors co‐localize in axons presynaptic boutons. interferes internalization of activated transfected heterologous cells. Consequently, transient association β‐arrestin2 enhanced prolonged, receptor‐mediated ERK1/2 signalling decreased. Because these actions,...
Abstract The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, goals include relief from posttraumatic disorders, anxiety, to support chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets other health conditions. Using an evidence-based approach, pharmacological investigation CB1R agonists is timely, aim provide chronically...
Metabotropic glutamate receptors (mGlu receptors), the Ca2+-sensing receptor, γ-aminobutyric acid type B receptors, and one group of pheromone constitute a unique family (also called 3) heptahelical receptors. This original shares no sequence similarity with any other G protein-coupled The identification comparison molecular determinants receptor/G protein coupling within different receptor families may help identify general rules involved in this protein/protein interaction. In order to...
We examined the role of G-protein coupled receptor kinase-2 (GRK2) in homologous desensitization mGlu4 metabotropic glutamate receptors transiently expressed human embryonic kidney (HEK) 293 cells. Receptor activation with agonist l-2-amino-4-phosphonobutanoate (l-AP4) stimulated at least two distinct signaling pathways: inhibition cAMP formation and mitogen-activated protein kinase (MAPK) pathway [assessed by Western blot analysis phosphorylated extracellular signal-regulated (ERK) 1 2]....
Specific domains of the G-protein α subunit have been shown to control coupling heptahelical receptors. The extreme N and C termini a region between α4 α5 helices are known determine selective interaction with metabotropic glutamate receptor 2 activated both mouse Gα15 its human homologue Gα16, whereas 8 only. C-terminal 20 amino acid residues identical Gα16 therefore unlikely be involved in selectivity. Our data reveal two regions on that inhibit 8. On three-dimensional model, found close...
Heptahelical receptor coupling selectivity to G-proteins is controlled by a large contact area that involves several portions of the and each subunit G-protein. In G-protein α subunit, C-terminal 5 residues, N terminus, αN-β1 α4–α5 loops play important roles. On side, both second third (i2 i3) intracellular as well tail probably these different regions It now accepted C terminus binds in cavity formed i2 i3 loops. Among various G-protein-coupled receptors (GPCRs), class III include...