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

Authors: Farhy-Tselnicker, Isabella  van Casteren, Adriana C M  Lee, Aletheia  Chang, Veronica T  Aricescu, A Radu  Allen, Nicola J 
Citation: Farhy-Tselnicker I, etal., Neuron. 2017 Oct 11;96(2):428-445.e13. doi: 10.1016/j.neuron.2017.09.053.
Pubmed: (View Article at PubMed) PMID:29024665
DOI: Full-text: DOI:10.1016/j.neuron.2017.09.053

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 d. 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.

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CRRD Object Information
CRRD ID: 13702141
Created: 2018-07-18
Species: All species
Last Modified: 2018-07-18
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.