Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC
Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC
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DOI：
10.1073/pnas.1104977108
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发表时间：
2011-08-09
影响因子：
11.1
通讯作者：
Eroglu, Cagla
中科院分区：
文献类型：
--
作者：
Kucukdereli, Hakan;Allen, Nicola J.;Eroglu, Cagla
星形胶质细胞通过分泌信号调节CNS中的突触连接。在这里，我们确定了两个星形胶质细胞分泌的蛋白质，hevin和hevin，作为调节兴奋性突触在体外和体内。Hevin诱导培养的大鼠视网膜神经节细胞之间的突触形成。hevin不是突触发生的，但特异性拮抗hevin的突触发生功能。在视网膜神经节细胞的突触靶点上级丘的星形胶质细胞中，Hevin和Hevin与兴奋性突触发生同时表达。Hevin基因敲除小鼠的兴奋性突触较少;相反，SPARC基因敲除小鼠的上级丘突触连接增加。此外，我们还发现hevin是视网膜丘突触结构成熟所必需的。这些结果表明，hevin作为一个积极的和hevin作为一个负调节突触的形成，并表示，通过调节hevin和hevin的相对水平，星形胶质细胞可能控制突触的形成，成熟和可塑性在体内。
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.