Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC
| Autor: | Hakan Kucukdereli, Laura M. Conatser, Ben A. Barres, E. Helene Sage, Chandrani Chakraborty, Gail Workman, Cagla Eroglu, Matthew S. Weaver, Ava Feng, Nicola J. Allen, Anthony T. Lee, M. Ilcim Ozlu |
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| Rok vydání: | 2011 |
| Předmět: |
Central Nervous System
Retinal Ganglion Cells Superior Colliculi Neurogenesis Synaptogenesis SPARCL1 Biology Retinal ganglion Rats Sprague-Dawley Mice medicine Animals Humans Osteonectin Extracellular Matrix Proteins Multidisciplinary Superior colliculus Calcium-Binding Proteins HEK 293 cells Protein Structure Tertiary Rats HEK293 Cells medicine.anatomical_structure Secretory protein PNAS Plus Astrocytes Culture Media Conditioned Synapses Excitatory postsynaptic potential Neuroscience Astrocyte |
| Zdroj: | Proceedings of the National Academy of Sciences. 108 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1104977108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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