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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kucukdereli, H; Allen, NJ; Lee, AT; Feng, A; Ozlu, MI; Conatser, LM; Chakraborty, C; Workman, G; Weaver, M; Sage, EH; Barres, BA; Eroglu, C

Published Date

  • August 9, 2011

Published In

Volume / Issue

  • 108 / 32

Start / End Page

  • E440 - E449

PubMed ID

  • 21788491

Pubmed Central ID

  • 21788491

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1104977108

Language

  • eng

Conference Location

  • United States