Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner
Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner
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DOI：
10.1111/j.1471-4159.2005.03224.x
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发表时间：
2005-08-01
影响因子：
4.7
通讯作者：
Smalheiser, NR
中科院分区：
文献类型：
--
作者：
Lugli, G;Larson, J;Smalheiser, NR
我们假设小RNA可能参与学习和记忆机制。由于树突棘在突触可塑性和学习中很重要，我们询问了小RNA形成中的限速酶dicer是否在树突棘中富集。在成年小鼠脑中，dicer和RNA诱导的沉默复合物（RISC）组分eIF2c在许多区域的主要神经元和一些中间神经元的体树突隔室中表达，并且dicer在树突棘和突触后密度（PSD）中富集。一部分dicer和eIF2c相互关联，并与脆性X智力低下蛋白（FMRP），通过免疫共沉淀评估。钙蛋白酶I治疗的重组切丁酶或免疫纯化的脑切丁酶引起RNA酶III活性的显着增加。纯化的PSD没有表现出RNA酶III活性，但钙蛋白酶引起从PSD中释放酶活性形式的dicer，以及eIF2c。海马切片的NMDA刺激，或突触神经体的钙处理，导致75 kDa的切丁酶片段出现在钙蛋白酶依赖的方式。这些发现支持了一种模型，即兴奋性突触处的急性神经元刺激增加细胞内钙，从而激活钙蛋白酶，释放与PSD结合的dicer和eIF2c。这支持了dicer可能参与突触可塑性的假设。
We have hypothesized that small RNAs may participate in learning and memory mechanisms. Because dendritic spines are important in synaptic plasticity and learning, we asked whether dicer, the rate-limiting enzyme in the formation of small RNAs, is enriched within dendritic spines. In adult mouse brain, dicer and the RNA-induced silencing complex (RISC) component eIF2c were expressed in the somatodendritic compartment of principal neurons and some interneurons in many regions, and dicer was enriched in dendritic spines and postsynaptic densities (PSDs). A portion of dicer and eIF2c were associated with each other and with fragile X mental retardation protein (FMRP), as assessed by co-immunoprecipitation. Calpain I treatment of recombinant dicer or immunopurified brain dicer caused a marked increase in RNAse III activity. Purified PSDs did not exhibit RNAse III activity, but calpain caused release of dicer from PSDs in an enzymatically active form, together with eIF2c. NMDA stimulation of hippocampal slices, or calcium treatment of synaptoneurosomes, caused a 75 kDa dicer fragment to appear in a calpain-dependent manner. The findings support a model whereby acute neuronal stimulation at excitatory synapses increases intracellular calcium, which activates calpain, which liberates dicer and eIF2c bound to PSDs. This supports the hypothesis that dicer could be involved in synaptic plasticity.