Journal Article

Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC

Chakraborty, Chandrani, Sage, E. Helene, Barres, Ben A, Conatser, Laura M, Lee, Anthony T, Feng, Ava, Eroglu, Cagla, Allen, Nicola J, Weaver, Matthew, Kucukdereli, Hakan, Workman, Gail, Ozlu, M. Ilcim

2011

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Animals / Astrocytes / Astrocytes - cytology / Astrocytes - drug effects / Astrocytes - secretion / Astrocytes - ultrastructure / Biological Sciences / Brain / Calcium-Binding Proteins - antagonists & inhibitors / Calcium-Binding Proteins - chemistry / Calcium-Binding Proteins - deficiency / Calcium-Binding Proteins - metabolism / Cells / Central nervous system / Central Nervous System - cytology / Central Nervous System - metabolism / Central Nervous System - ultrastructure / Culture Media, Conditioned - pharmacology / Extracellular Matrix Proteins - antagonists & inhibitors / Extracellular Matrix Proteins - chemistry / Extracellular Matrix Proteins - deficiency / Extracellular Matrix Proteins - metabolism / ganglia / HEK293 Cells / Humans / Mice / Neural networks / Neurogenesis - drug effects / Osteonectin / Osteonectin - chemistry / Osteonectin - deficiency / Osteonectin - metabolism / PNAS Plus / Protein Structure, Tertiary / Proteins / Rats / Rats, Sprague-Dawley / Retinal ganglion cells / Retinal Ganglion Cells - cytology / Retinal Ganglion Cells - drug effects / Retinal Ganglion Cells - metabolism / Retinal Ganglion Cells - ultrastructure / Rodents / Superior Colliculi - cytology / Superior Colliculi - drug effects / Superior Colliculi - metabolism / Superior Colliculi - ultrastructure / Superior colliculus / synapse / Synapses / Synapses - drug effects / Synapses - metabolism / Synapses - ultrastructure / Synaptogenesis