Neuron
Volume 96, Issue 2, 11 October 2017, Pages 428-445.e13
Journal home page for Neuron

Article
Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation

https://doi.org/10.1016/j.neuron.2017.09.053Get rights and content
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Highlights

  • Astrocyte-secreted Gpc4 induces release of NP1 from neurons

  • Release of NP1 is mediated through Gpc4 interaction with presynaptic RPTPδ

  • Gpc4 or RPTPδ KO causes presynaptic NP1 retention and decreased synapse number

  • Astrocytic release of Gpc4 provides spatial and temporal cues for synaptogenesis

Summary

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.

Keywords

astrocyte
glia
synapse
AMPAR
development
glypican
neuronal pentraxin 1

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