The hnRNP and cytoskeletal protein raver1 contributes to synaptic plasticity
The hnRNP and cytoskeletal protein raver1 contributes to synaptic plasticity
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DOI：
10.1016/j.yexcr.2007.10.022
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发表时间：
2008-03-10
影响因子：
3.7
通讯作者：
Arnold, Hans-Henning
中科院分区：
文献类型：
--
作者：
Lahmann, Ines;Fabienke, Manuela;Arnold, Hans-Henning
Rver1是一种hnRNP蛋白，它与普遍存在的剪接调节因子PTB相互作用，并与细胞骨架结合。如α-肌动蛋白和纽蛋白/偏钙蛋白等成分。细胞培养实验表明，raver1在PTB调节的剪接反应中作为辅助抑制物发挥作用，从而可能增加蛋白质组的复杂性。为了确定raver1在体内的作用，我们在小鼠中通过定向破坏使该基因失活。在这里，我们报告了raver1缺陷小鼠有规律地发育到成年，没有表现出明显的解剖学或行为缺陷。与这一概念一致，来自raver1基因缺失小鼠的细胞与野生型细胞难以区分，在培养中表现出正常的生长、运动和细胞骨架结构。此外，外显子的选择性剪接，包括α-原肌球蛋白的模型外显子3，在突变小鼠中没有明显变化，这表明在小鼠发育过程中，raver1在PTB介导的外显子抑制中的作用并不是绝对必要的。然而，有趣的是，Rver1的缺失导致急性海马片上突触的可塑性显著降低，这是由突变神经元中显著降低的LTP和LTD引起的。我们的结果提供了证据，表明raver1可能通过转录后机制控制神经元突触可塑性，特别是晚期LTP，从而在神经元突触可塑性调节中发挥重要作用。(C)2007 Elsevier Inc.保留所有权利。
Raver1 is an hnRNP protein that interacts with the ubiquitous splicing regulator PTB and binds to cytoskeletal. components like a-actinin and vinculin/metavinculin. Cell culture experiments suggested that raver1 functions as corepressor in PTB-regulated splicing reactions and may thereby increase proteome complexity. To determine the role of raver1 in vivo, we inactivated the gene by targeted disruption in the mouse. Here we report that raver1-deficient mice develop regularly to adulthood and show no obvious anatomical or behavioral defects. In keeping with this notion, cells from raver1-null mice were indistinguishable from wild type cells and displayed normal growth, motility, and cytoskeletal architecture in culture. Moreover, alternative splicing of exons, including the model exon 3 of alpha-tropomyosin, was not markedly changed in mutant mice, suggesting that the role of raver1 for PTB-mediated exon repression is not absolutely required to generate splice variants during mouse development. Interestingly however, loss of raver1 caused significantly reduced plasticity of synapses on acute hippocampal slices, as elicited by electrophysiological measurements of markedly lower LTP and LTD in mutant neurons. Our results provide evidence that raver1 may play an important role for the regulation of neuronal synaptic plasticity, possibly by controlling especially the late LTP via posttranscriptional mechanisms. (C) 2007 Elsevier Inc. All rights reserved.