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

神经元树突和树突棘表现出极其多样的结构。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（易位于脂肪肉瘤），先前被认为是hnRNP复合物的一个组成部分，意外地在成熟的海马锥体神经元中显示出体树突定位。TLS作为rna -蛋白复合物转移到树突上，不仅通过微管，而且通过肌动蛋白丝被募集到树突上。在成熟的海马锥体神经元中，mGluR5激活后，TLS在兴奋性突触后的棘中积累，并伴随着树突中RNA含量的增加。与体外研究一致，tls缺失海马锥体神经元表现出异常的脊柱形态和较低的脊柱密度。我们进一步证明，与野生型树突相比，在mglur激活后，TLS-null神经元树突的RNA载货量减少，并特别鉴定了一种肌动蛋白稳定蛋白Nd1-L作为tls相关的RNA载货。TLS参与mGluR5激活诱导的树突棘mRNA分选，调控脊柱形态稳定突触结构，可能是通过肌动蛋白网络实现的，提示TLS是脊柱成熟和兴奋性突触后位点可塑性的必要条件。

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.