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Neto-Mediated Intracellular Interactions Shape Postsynaptic Composition at the Neuromuscular Junction


Ionotropic receptors assembled from different subunits have strikingly different properties and uses. In mammalian brain, the molecular mechanisms controlling the subunit composition of glutamate receptors are critical for the formation of neural circuits and for the long-term plasticity underlying learning and memory. Here we investigate how subunit composition is regulated at the Drosophila neuromuscular junction (NMJ), a synapse similar in composition and physiology to mammalian AMPA/Kainate synapses. We find that an auxiliary protein, Neto, which is essential for functional receptors, has a key role in controlling which flavor of glutamate receptors will be at the synapses. In flies, synapse strength and plasticity is modulated by the interplay between two receptor subtypes, A and B. Mutations that eliminate or truncate the Neto-β isoform fail to accumulate the type-A receptors, as well as other postsynaptic proteins important for the synaptic stabilization of type-A receptors. This result indicates that Neto may use its cytoplasmic domains as signaling hubs and organizing platforms to sculpt postsynaptic composition. Neto proteins modulate the formation and function of glutamatergic synapses from worms to humans. Our findings expand the repertoire of Neto proteins and illustrate the richness in synapse modulation brought about by the growing family of auxiliary proteins.


Vyšlo v časopise: Neto-Mediated Intracellular Interactions Shape Postsynaptic Composition at the Neuromuscular Junction. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005191
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005191

Souhrn

Ionotropic receptors assembled from different subunits have strikingly different properties and uses. In mammalian brain, the molecular mechanisms controlling the subunit composition of glutamate receptors are critical for the formation of neural circuits and for the long-term plasticity underlying learning and memory. Here we investigate how subunit composition is regulated at the Drosophila neuromuscular junction (NMJ), a synapse similar in composition and physiology to mammalian AMPA/Kainate synapses. We find that an auxiliary protein, Neto, which is essential for functional receptors, has a key role in controlling which flavor of glutamate receptors will be at the synapses. In flies, synapse strength and plasticity is modulated by the interplay between two receptor subtypes, A and B. Mutations that eliminate or truncate the Neto-β isoform fail to accumulate the type-A receptors, as well as other postsynaptic proteins important for the synaptic stabilization of type-A receptors. This result indicates that Neto may use its cytoplasmic domains as signaling hubs and organizing platforms to sculpt postsynaptic composition. Neto proteins modulate the formation and function of glutamatergic synapses from worms to humans. Our findings expand the repertoire of Neto proteins and illustrate the richness in synapse modulation brought about by the growing family of auxiliary proteins.


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