Postsynaptic gephyrin clustering controls the development of adult-born granule cells in the olfactory bulb
| Autor: | Deprez, F., Pallotto, M., Vogt, F., Grabiec, M., Virtanen, M. A., Tyagarajan, S. K., Panzanelli, Patrizia, Fritschy, J. M. |
|---|---|
| Přispěvatelé: | University of Zurich, Fritschy, Jean-Marc |
| Rok vydání: | 2015 |
| Předmět: |
Male
Cell Survival Vesicular Inhibitory Amino Acid Transport Proteins Neurogenesis Green Fluorescent Proteins 10050 Institute of Pharmacology and Toxicology 610 Medicine & health Mice Cell Movement Transduction Genetic Animals Humans Neurons General Neuroscience Age Factors 2800 General Neuroscience Membrane Proteins Post-Synaptic Density Dendrites Receptors GABA-A Olfactory Bulb HEK293 Cells Mutation Vesicular Glutamate Transport Protein 1 570 Life sciences biology Carrier Proteins |
| Zdroj: | The Journal of comparative neurology |
| ISSN: | 1096-9861 |
| Popis: | In adult rodent olfactory bulb, GABAergic signaling regulates migration, differentiation, and synaptic integration of newborn granule cells (GCs), migrating from the subventricular zone. Here we show that these effects depend on the formation of a postsynaptic scaffold organized by gephyrin-the main scaffolding protein of GABAergic synapses, which anchors receptors and signaling molecules to the postsynaptic density-and are regulated by the phosphorylation status of gephyrin. Using lentiviral vectors to selectively transfect adult-born GCs, we observed that overexpression of the phospho-deficient gephyrin mutant eGFP-gephyrin(S270A), which facilitates the formation of supernumerary GABAergic synapses in vitro, favors dendritic branching and the formation of transient GABAergic synapses on spines, identified by the presence of α2-GABAA Rs. In contrast, overexpression of the dominant-negative eGFP-gephyrin(L2B) (a chimera that is enzymatically active but clustering defective), curtailed dendritic growth, spine formation, and long-term survival of GCs, pointing to the essential role of gephyrin cluster formation for its function. We could exclude any gephyrin overexpression artifacts, as GCs infected with eGFP-gephyrin were comparable to those infected with eGFP alone. The opposite effects induced by the two gephyrin mutant constructs indicate that the gephyrin scaffold at GABAergic synapses orchestrates signaling cascades acting on the cytoskeleton to regulate neuronal growth and synapse formation. Specifically, gephyrin phosphorylation emerges as a novel mechanism regulating morphological differentiation and long-term survival of adult-born olfactory bulb neurons. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text