Mechanism for neurotransmitter-receptor matching
| Autor: | Nicholas C. Spitzer, Dena R. Hammond-Weinberger, Alex Glavis-Bloom, Yunxin Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Xenopus receptor specification Glutamic Acid Receptors N-Methyl-D-Aspartate 03 medical and health sciences 0302 clinical medicine Postsynaptic potential Neurotransmitter receptor Receptors Animals Mitogen-Activated Protein Kinase 8 Receptor development Neurons Muscle Cells Neurotransmitter Agents Multidisciplinary Chemistry Glutamate receptor Biological Sciences Cell biology Biophysics and Computational Biology 030104 developmental biology Metabotropic glutamate receptor glutamate receptors plasticity Physical Sciences Synapses NMDA receptor Ionotropic glutamate receptor Calcium Female neurotransmitter respecification 030217 neurology & neurosurgery Ionotropic effect Neuroscience N-Methyl-D-Aspartate |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 8 Proceedings of the National Academy of Sciences of the United States of America |
| Popis: | Significance Neurotransmitter switching generally involves replacement of an excitatory transmitter with an inhibitory transmitter or vice versa and has been linked to changes in animal behavior. There are corresponding switches in postsynaptic receptors that enable continued function of the circuit, but the mechanism by which receptor expression is regulated in this context was unknown. Sustained exposure to the neurotransmitter glutamate during development is both necessary and sufficient for the upregulation of ionotropic glutamate receptors in vertebrate striated skeletal muscle cells. This finding suggests a basis by which neurotransmitter release up-regulates expression of matching receptors at newly formed synapses during development of the nervous system and in response to neurotransmitter switching at established synapses. Synaptic communication requires the expression of functional postsynaptic receptors that match the presynaptically released neurotransmitter. The ability of neurons to switch the transmitter they release is increasingly well documented, and these switches require changes in the postsynaptic receptor population. Although the activity-dependent molecular mechanism of neurotransmitter switching is increasingly well understood, the basis of specification of postsynaptic neurotransmitter receptors matching the newly expressed transmitter is unknown. Using a functional assay, we show that sustained application of glutamate to embryonic vertebrate skeletal muscle cells cultured before innervation is necessary and sufficient to up-regulate ionotropic glutamate receptors from a pool of different receptors expressed at low levels. Up-regulation of these ionotropic receptors is independent of signaling by metabotropic glutamate receptors. Both imaging of glutamate-induced calcium elevations and Western blots reveal ionotropic glutamate receptor expression prior to immunocytochemical detection. Sustained application of glutamate to skeletal myotomes in vivo is necessary and sufficient for up-regulation of membrane expression of the GluN1 NMDA receptor subunit. Pharmacological antagonists and morpholinos implicate p38 and Jun kinases and MEF2C in the signal cascade leading to ionotropic glutamate receptor expression. The results suggest a mechanism by which neuronal release of transmitter up-regulates postsynaptic expression of appropriate transmitter receptors following neurotransmitter switching and may contribute to the proper expression of receptors at the time of initial innervation. |
| Databáze: | OpenAIRE |
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