Functional analysis of an RNA-binding protein, TLS, in neuronal dendrites.

神经元树突与树突棘一起表现出非常多样的结构。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。TLS（易位在脂肪肉瘤），以前确定为hnRNP复合物的一个组成部分，出乎意料地显示体树突定位在成熟的海马锥体神经元。TLS作为RNA-蛋白质复合物被转运到树突，并且不仅通过微管而且通过肌动蛋白丝被募集到树突。在成熟的海马锥体神经元中，TLS积累在兴奋性突触后的棘mGluR 5激活后，这是伴随着树突中的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。我们进一步证明，与野生型树突相比，在mGluR激活后，TLS无效神经元树突的RNA货物减少，并特别鉴定了一种肌动蛋白稳定蛋白Nd 1-L作为TLS相关的RNA货物。TLS参与mGluR 5激活诱导的树突棘的mRNA分选，并可能通过肌动蛋白网络调节树突棘的形态以稳定突触结构，提示TLS对树突棘的成熟和兴奋性突触后位点的可塑性是必需的。

Neuronal dendrites, together with dendritic spines, exhibit enormously diverse structure. Selective targeting and local translation of mRNAs in dendritic spines have been implicated in synapse remodeling or synaptic plasticity. TLS (translocated in liposarcoma), previously identified as a component of hnRNP complexes, unexpectedly showed somatodendritic localization in mature hippocampal pyramidal neurons. TLS was translocated to dendrites as an RNA-protein complex 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 mGluR5 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. We further demonstrated that TLS-null neuronal dendrites had decreased RNA cargo following mGluR-activation compared to wild-type dendrites and specifically identified an actin-stabilizing protein, Nd1-L, as a TLS-associated RNA cargo. TLS participates in mRNA sorting to the dendritic spines induced by mGluR5 activation and regulates spine morphology to stabilize the synaptic structure probably through actin-network, suggesting that TLS is necessary for spine maturation and the plasticity of excitatory postsynaptic sites.