Filamin A-interacting protein (FILIP) is a region-specific modulator of myosin 2b and controls spine morphology and NMDA receptor accumulation.

Filamin A-interacting protein (FILIP) is a region-specific modulator of myosin 2b and controls spine morphology and NMDA receptor accumulation.
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DOI:
10.1038/srep06353
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发表时间:
2014-09-15
期刊:
影响因子:
4.6
通讯作者:
Sato M
Sato M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yagi H;Nagano T;Xie MJ;Ikeda H;Kuroda K;Komada M;Iguchi T;Tariqur RM;Morikubo S;Noguchi K;Murase K;Okabe M;Sato M

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学习和记忆取决于神经棘的形态和功能变化。非肌肉肌球蛋白 2b 调节长时程增强诱导下游的肌动蛋白动力学。然而,肌球蛋白2b在脊柱中的调节机制尚未完全阐明。在这里,我们证明细丝蛋白 A 相互作用蛋白 (FILIP) 参与神经棘形态的控制,并且在大脑中有限表达。 FILIP 结合在非肌肉肌球蛋白重链 IIb(肌球蛋白 2b 的重要组成部分)的 ATP 酶结构域附近,并通过干扰其肌动蛋白结合活性来修饰肌球蛋白 2b 的功能。此外,FILIP 改变了棘中肌球蛋白 2b 的亚细胞分布。此外,NMDA 受体的亚基在表达 FILIP 的神经元中分布不同,并且 FILIP 敲除小鼠中的兴奋传播发生了改变。这些结果表明 FILIP 是一种新型的、区域特异性的肌球蛋白 2b 调节剂。
Learning and memory depend on morphological and functional changes to neural spines. Non-muscle myosin 2b regulates actin dynamics downstream of long-term potentiation induction. However, the mechanism by which myosin 2b is regulated in the spine has not been fully elucidated. Here, we show that filamin A-interacting protein (FILIP) is involved in the control of neural spine morphology and is limitedly expressed in the brain. FILIP bound near the ATPase domain of non-muscle myosin heavy chain IIb, an essential component of myosin 2b, and modified the function of myosin 2b by interfering with its actin-binding activity. In addition, FILIP altered the subcellular distribution of myosin 2b in spines. Moreover, subunits of the NMDA receptor were differently distributed in FILIP-expressing neurons, and excitation propagation was altered in FILIP-knockout mice. These results indicate that FILIP is a novel, region-specific modulator of myosin 2b.
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