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Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the Neuromuscular Junction


Synapse development is initiated by genetic programs, but is coordinated by neuronal activity, by communication between the pre- and postsynaptic compartments, and by cellular signals that integrate the status of the whole organisms and its developmental progression. The molecular mechanisms underlining these processes are poorly understood. In particular, how neurotransmitter receptors are recruited and stabilized at central synapses remain the subject of intense research. The Drosophila NMJ is a glutamatergic synapse similar in composition and physiology with mammalian central excitatory synapses. Like mammals, Drosophila utilizes auxiliary subunit(s) to modulate the formation and function of glutamatergic synapses. We have previously reported that Neto is an auxiliary protein essential for functional glutamate receptors and for organization of postsynaptic specializations. Here we report that synapse assembly and NMJ development are exquisitely sensitive to postsynaptic Neto levels. Furthermore, we show that Neto activity is controlled by Furin-type proteases, which regulate the processing and maturation of many developmentally important proteins, from growth factors and neuropeptides to extracellular matrix components. Such concerted control may serve to coordinate synapse assembly with synapse growth and developmental progression.


Vyšlo v časopise: Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the Neuromuscular Junction. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004988
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004988

Souhrn

Synapse development is initiated by genetic programs, but is coordinated by neuronal activity, by communication between the pre- and postsynaptic compartments, and by cellular signals that integrate the status of the whole organisms and its developmental progression. The molecular mechanisms underlining these processes are poorly understood. In particular, how neurotransmitter receptors are recruited and stabilized at central synapses remain the subject of intense research. The Drosophila NMJ is a glutamatergic synapse similar in composition and physiology with mammalian central excitatory synapses. Like mammals, Drosophila utilizes auxiliary subunit(s) to modulate the formation and function of glutamatergic synapses. We have previously reported that Neto is an auxiliary protein essential for functional glutamate receptors and for organization of postsynaptic specializations. Here we report that synapse assembly and NMJ development are exquisitely sensitive to postsynaptic Neto levels. Furthermore, we show that Neto activity is controlled by Furin-type proteases, which regulate the processing and maturation of many developmentally important proteins, from growth factors and neuropeptides to extracellular matrix components. Such concerted control may serve to coordinate synapse assembly with synapse growth and developmental progression.


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