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

作者：Hakan Kucukdereli, Nicola J. Allen, Anthony T. Lee, Ava Feng, M. Ilcim Ozlu, Laura Conatser, Chandrani Chakraborty, Gail Workman, Matthew D. Weaver, E. Helene Sage, Ben A. Barres, Çağla Eroğlu · 发表于：Proceedings of the National Academy of Sciences · 年份：2011 · DOI：10.1073/pnas.1104977108 · 被引用次数：665 · 研究领域：Bone and Dental Protein Studies、Barrier Structure and Function Studies、Amino Acid Enzymes and Metabolism

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.