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Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation.
- Source :
-
Neuron [Neuron] 2017 Oct 11; Vol. 96 (2), pp. 428-445.e13. - Publication Year :
- 2017
-
Abstract
- The generation of precise synaptic connections between developing neurons is critical to the formation of functional neural circuits. Astrocyte-secreted glypican 4 induces formation of active excitatory synapses by recruiting AMPA glutamate receptors to the postsynaptic cell surface. We now identify the molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces release of the AMPA receptor clustering factor neuronal pentraxin 1 from presynaptic terminals by signaling through presynaptic protein tyrosine phosphatase receptor δ. Pentraxin then accumulates AMPA receptors on the postsynaptic terminal forming functional synapses. Our findings reveal a signaling pathway that regulates synaptic activity during central nervous system development and demonstrates a role for astrocytes as organizers of active synaptic connections by coordinating both pre and post synaptic neurons. As mutations in glypicans are associated with neurological disorders, such as autism and schizophrenia, this signaling cascade offers new avenues to modulate synaptic function in disease.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
C-Reactive Protein genetics
Cells, Cultured
Female
Glypicans
HEK293 Cells
Heparan Sulfate Proteoglycans physiology
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins genetics
Rats
Rats, Sprague-Dawley
Receptors, AMPA metabolism
Retinal Ganglion Cells metabolism
Synapses genetics
Astrocytes metabolism
Axons metabolism
C-Reactive Protein metabolism
Heparan Sulfate Proteoglycans metabolism
Nerve Tissue Proteins metabolism
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 96
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 29024665
- Full Text :
- https://doi.org/10.1016/j.neuron.2017.09.053