RGD Reference Report - Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation. - Rat Genome Database

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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.
RGD ID: 13702141
Pubmed: PMID:29024665   (View Abstract at PubMed)
PMCID: PMC5663462   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2017.09.053   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nptx1Ratglutamatergic synapse is_active_inEXP PMID:29024665SynGO 
Nptx1Ratglutamatergic synapse is_active_inIDA PMID:29024665SynGO 
Nptx1Ratglutamatergic synapse is_active_inIMP PMID:29024665SynGO 
PtprdRatglutamatergic synapse is_active_inEXP PMID:29024665SynGO 
PtprdRatglutamatergic synapse is_active_inIDA PMID:29024665SynGO 
Nptx1Ratsynaptic cleft is_active_inIDA PMID:29024665SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Nptx1  (neuronal pentraxin 1)
Ptprd  (protein tyrosine phosphatase, receptor type, D)


Additional Information