Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology.
Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology.
复制标题
DOI：
10.1083/jcb.201008050
复制
发表时间：
2011-05-16
期刊：
影响因子：
--
通讯作者：
Hsueh YP
中科院分区：
文献类型：
--
作者：
Chen CY;Lin CW;Chang CY;Jiang ST;Hsueh YP
syndecan Sds2和先天免疫抑制剂Sarm1共同作用，并以不同的途径促进适当的神经元形态发生。树突分化是神经元分化的重要过程。在这里，我们证明syndecan-2 （Sdc2）是一种突触硫酸肝素蛋白聚糖，可触发树突丝状伪足和脊柱形成，调节培养的海马神经元的树突树突化。这一过程由无菌α和含有TIR基序的1蛋白（Sarm1）控制，Sarm1是toll样受体3 （TLR3）在先天免疫信号传导中的负调节因子。我们发现Sarm1与Sdc2相互作用并接收来自Sdc2的信号，并通过MKK4-JNK途径控制树突化。在敲除Sarm1的小鼠中，神经元的树突乔木比野生型的小鼠更简单。除了作用于Sdc2的下游，Sarm1的表达早于Sdc2，这表明它在神经元形态发生中具有多种作用。具体来说，它是树突的起始和延伸、轴突的生长和神经元极化所必需的。这些功能可能涉及Sarm1介导的微管稳定性调节，因为Sarm1影响微管蛋白乙酰化。本研究揭示了Sarm1在神经元形态发生中的分子机制。
The syndecan Sds2 and the innate immunity inhibitor Sarm1 function together and in distinct pathways to promote proper neuronal morphogenesis. Dendritic arborization is a critical neuronal differentiation process. Here, we demonstrate that syndecan-2 (Sdc2), a synaptic heparan sulfate proteoglycan that triggers dendritic filopodia and spine formation, regulates dendritic arborization in cultured hippocampal neurons. This process is controlled by sterile α and TIR motif–containing 1 protein (Sarm1), a negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling. We show that Sarm1 interacts with and receives signal from Sdc2 and controls dendritic arborization through the MKK4–JNK pathway. In Sarm1 knockdown mice, dendritic arbors of neurons were less complex than those of wild-type littermates. In addition to acting downstream of Sdc2, Sarm1 is expressed earlier than Sdc2, which suggests that it has multiple roles in neuronal morphogenesis. Specifically, it is required for proper initiation and elongation of dendrites, axonal outgrowth, and neuronal polarization. These functions likely involve Sarm1-mediated regulation of microtubule stability, as Sarm1 influenced tubulin acetylation. This study thus reveals the molecular mechanism underlying the action of Sarm1 in neuronal morphogenesis.
登录
查看更多内容
影响因子：
9.2
作者：
Dajas-Ballador, Federico;Jones, Emma V.;Whitmarsh, Alan J.
通讯作者：
Whitmarsh, Alan J.
影响因子：
16.2
作者：
Ehninger, Dan;Li, Weidong;Fox, Kevin;Stryker, Michael P.;Silva, Alcino J.
通讯作者：
Silva, Alcino J.
DOI：
10.1083/jcb.200712094
发表时间：
2008-07-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chao HW;Hong CJ;Huang TN;Lin YL;Hsueh YP
通讯作者：
Hsueh YP
DOI：
10.1083/jcb.142.1.139
发表时间：
1998-07-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hsueh YP;Yang FC;Kharazia V;Naisbitt S;Cohen AR;Weinberg RJ;Sheng M
通讯作者：
Sheng M
影响因子：
15.3
作者：
Kim, Younghwa;Zhou, Ping;Ding, Aihao
通讯作者：
Ding, Aihao