In this issue of Neuron, Fossati et al. (2019) report a new constellation of players regulating inhibitory synaptogenesis. They show that GluD1, through a non-canonical ionotropic-independent mechanism, controls GABAergic synapse formation via trans-synaptic interactions mediated by extracellular cerebellin-4. They identify ARHGEF12 and PPP1R12A as GluD1 intracellular interactors and downstream effectors.
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http://dx.doi.org/10.1016/j.neuron.2019.11.025 | DOI Listing |
Sci Rep
January 2025
Department of Histology and Embryology, Ankara University School of Medicine, Ankara, Turkey.
NMDAR antagonists, such as memantine and ketamine, have shown efficacy in treating neurodegenerative diseases and major depression. The mechanism by which these drugs correct the aforementioned diseases is still unknown. Our study reveals that these antagonists significantly enhance 20S proteasome activity, crucial for degrading intrinsically disordered, oxidatively damaged, or misfolded proteins, factors pivotal in neurodegenerative diseases like Alzheimer's and Parkinson's.
View Article and Find Full Text PDFNat Commun
January 2025
IGF, Université de Montpellier, CNRS, INSERM, 34094, Montpellier, France.
The metabotropic glutamate receptors (mGlus) are class C G protein-coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate. The architecture of mGlu receptor comprises an extracellular Venus-Fly Trap domain (VFT) connected to the transmembrane domain (7TM) through a Cysteine-Rich Domain (CRD). The binding of L-glutamate in the VFTs and subsequent conformational change results in the signal being transmitted to the 7TM inducing G protein binding and activation.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Aim: Somatostatin from pancreatic δ-cells is a paracrine regulator of insulin and glucagon secretion, but the release kinetics and whether secretion is altered in diabetes is unclear. This study aimed to improve understanding of somatostatin secretion by developing a tool for real-time detection of somatostatin release from individual pancreatic islets.
Methods: Reporter cells responding to somatostatin with cytoplasmic Ca concentration ([Ca]) changes were generated by co-expressing somatostatin receptor SSTR2, the G-protein Gα15 and a fluorescent Ca sensor in HeLa cells.
The medial habenula (MHb)-interpeduncular nucleus (IPN) pathway plays an important role in information transferring between the forebrain and the midbrain. The MHb-IPN pathway has been implicated in the regulation of fear behavior and nicotine addiction. The synapses between the ventral MHb and the IPN show a unique property, i.
View Article and Find Full Text PDFJ Comp Neurol
January 2025
Graduate Program in Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia, USA.
Glutamate delta receptor 1 (GluD1) is a unique synaptogenic molecule expressed at excitatory and inhibitory synapses. The lateral habenula (LHb), a subcortical structure that regulates negative reward prediction error and major monoaminergic systems, is enriched in GluD1. LHb dysfunction has been implicated in psychiatric disorders such as depression and schizophrenia, both of which are associated with GRID1, the gene that encodes GluD1.
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