The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology
The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology
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DOI：
10.1016/j.cub.2005.01.058
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发表时间：
2005-03-29
期刊：
影响因子：
9.2
通讯作者：
Takumi, T
中科院分区：
文献类型：
--
作者：
Fujii, R;Okabe, S;Takumi, T
神经元树突与树突棘一起表现出极其多样化的结构[1]。树突棘中 mRNA 的选择性靶向和局部翻译与突触重塑或突触可塑性有关 [2, 3]。 mRNA 转运至突触后位点的机制是局部树突翻译中的一个基本问题 [4, 5]。 TLS（在脂肪肉瘤中易位）先前被鉴定为 hnRNP 复合物的组成部分，出人意料地在成熟海马锥体神经元中显示出体树突定位。在本研究中，TLS 被转移到树突，并且不仅通过微管而且通过肌动蛋白丝被招募到树突。在成熟的海马锥体神经元中，mGIuR5 激活后，TLS 在兴奋性突触后的棘中积累，同时树突中 RNA 含量增加。与体外研究一致，TLS 无效的海马锥体神经元表现出异常的棘形态和较低的棘密度。我们的结果表明，TLS 参与 mGIuR5 激活诱导的树突棘 mRNA 分选，并调节树突棘形态以稳定突触结构。
Neuronal dendrites, together with dendritic spines, exhibit enormously diverse structure [1]. Selective targeting and local translation of mRNAs in dendritic spines have been implicated in synapse remodeling or synaptic plasticity [2, 3]. The mechanism of mRNA transport to the postsynaptic site is a fundamental question in local dendritic translation [4, 5]. TLS (translocated in liposarcoma), previously identified as a component of hnRNP complexes, unexpectedly showed somatodendritic localization in mature hippocampal pyramidal neurons. In the present study, TLS was translocated to dendrites and was recruited to dendrites not only via microtubules but also via actin filaments. In mature hippocampal pyramidal neurons, TLS accumulated in the spines at excitatory postsynapses upon mGIuR5 activation, which was accompanied by an increased RNA content in dendrites. Consistent with the in vitro studies, TLS-null hippocampal pyramidal neurons exhibited abnormal spine morphology and lower spine density. Our results indicate that TLS participates in mRNA sorting to the dendritic spines induced by mGIuR5 activation and regulates spine morphology to stabilize the synaptic structure.