title: Astrocytes control glutamate receptor levels at developing synapses through SPARC-beta-integrin interactions.
abstract: Neurons recruit numerous mechanisms to facilitate the development of synaptic connections. However, little is known about activity-dependent mechanisms that control the timing and fidelity of this process. Here we describe a novel pathway used by neurons to regulate glutamate receptors at maturing central synapses. This pathway relies on communication between neurons and astrocytes and the ability of astrocytes to release the factor SPARC (secreted protein, acidic and rich in cysteine). SPARC expression is dynamically regulated and plays a critical role in determining the level of synaptic AMPARs. SPARC ablation in mice increases excitatory synapse function, causes an abnormal accumulation of surface AMPARs at synapses, and impairs synaptic plasticity during development. We further demonstrate that SPARC inhibits the properties of neuronal β3-integrin complexes, which are intimately coupled to AMPAR stabilization at synapses. Thus neuron-glial signals control glutamate receptor levels at developing synapses to enable activity-driven modifications of synaptic strength.
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Emma V
authors.initials: EV
authors.lastname: Jones
authors.forename: Yann
authors.initials: Y
authors.lastname: Bernardinelli
authors.forename: Yiu Chung
authors.initials: YC
authors.lastname: Tse
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chierzi
authors.forename: Tak Pan
authors.initials: TP
authors.lastname: Wong
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D039641:Integrin beta Chains; D015676:Osteonectin; D017470:Receptors, Glutamate