Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling.
Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling.
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DOI：
10.1371/journal.pone.0133115
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ip NY
中科院分区：
文献类型：
--
作者：
Chen Y;Liang Z;Fei E;Chen Y;Zhou X;Fang W;Fu WY;Fu AK;Ip NY
在发育过程中，支架蛋白作为重要的平台，用于协调信号复合物，将细胞外刺激转化为细胞内反应，调节树突棘的形态和功能。轴蛋白（“轴抑制剂”）是与特定突触蛋白相互作用的经典Wnt信号传导中的关键支架蛋白。然而，这些蛋白质-蛋白质相互作用在树突棘形态和突触调节中的细胞功能尚不清楚。在这里，我们报告，轴蛋白是丰富的突触组分，共定位与突触后标记PSD-95在培养的海马神经元，并与信号蛋白Ca 2 +/钙调素依赖性蛋白激酶II（CaMKII）在突触体组分相互作用。在培养的神经元或完整的海马CA 1区的shRNA的轴突耗竭显着降低树突棘密度。有趣的是，Axin敲除神经元中有缺陷的树突棘形态发生可以通过小Rho-GTdR Cdc 42的过表达来恢复，其活性受CaMKII调节。此外，Axin的药理学稳定导致树突棘数量增加和自发神经传递，而海马神经元中Axin的稳定减少了树突棘的消除。总之，我们的研究结果表明，Axin通过Cdc 42依赖的细胞骨架重组促进树突棘稳定。
During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin (“axis inhibitor”) is a key scaffold protein in canonical Wnt signaling that interacts with specific synaptic proteins. However, the cellular functions of these protein–protein interactions in dendritic spine morphology and synaptic regulation are unclear. Here, we report that Axin protein is enriched in synaptic fractions, colocalizes with the postsynaptic marker PSD-95 in cultured hippocampal neurons, and interacts with a signaling protein Ca2+/calmodulin-dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced dendritic spine density. Intriguingly, the defective dendritic spine morphogenesis in Axin-knockdown neurons could be restored by overexpression of the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover, pharmacological stabilization of Axin resulted in increased dendritic spine number and spontaneous neurotransmission, while Axin stabilization in hippocampal neurons reduced the elimination of dendritic spines. Taken together, our findings suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent cytoskeletal reorganization.