title: Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC.
abstract: Astrocytes regulate synaptic connectivity in the CNS through secreted signals. Here we identified two astrocyte-secreted proteins, hevin and SPARC, as regulators of excitatory synaptogenesis in vitro and in vivo. Hevin induces the formation of synapses between cultured rat retinal ganglion cells. SPARC is not synaptogenic, but specifically antagonizes synaptogenic function of hevin. Hevin and SPARC are expressed by astrocytes in the superior colliculus, the synaptic target of retinal ganglion cells, concurrent with the excitatory synaptogenesis. Hevin-null mice had fewer excitatory synapses; conversely, SPARC-null mice had increased synaptic connections in the superior colliculus. Furthermore, we found that hevin is required for the structural maturation of the retinocollicular synapses. These results identify hevin as a positive and SPARC as a negative regulator of synapse formation and signify that, through regulation of relative levels of hevin and SPARC, astrocytes might control the formation, maturation, and plasticity of synapses in vivo.
authors.affiliation: Cell Biology Department, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kucukdereli
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Allen
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Lee
authors.forename: Ava
authors.initials: A
authors.lastname: Feng
authors.forename: M Ilcim
authors.initials: MI
authors.lastname: Ozlu
authors.forename: Laura M
authors.initials: LM
authors.lastname: Conatser
authors.forename: Chandrani
authors.initials: C
authors.lastname: Chakraborty
authors.forename: Gail
authors.initials: G
authors.lastname: Workman
authors.forename: Matthew
authors.initials: M
authors.lastname: Weaver
authors.forename: E Helene
authors.initials: EH
authors.lastname: Sage
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
authors.forename: Cagla
authors.initials: C
authors.lastname: Eroglu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects; D015676:Osteonectin / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D015676:Osteonectin; C503127:Sparcl1 protein, mouse