MSAP is a novel MIR-interacting protein that enhances neurite outgrowth and increases myosin regulatory light chain
MSAP is a novel MIR-interacting protein that enhances neurite outgrowth and increases myosin regulatory light chain
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DOI：
10.1074/jbc.m306271200
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发表时间：
2003-09-12
影响因子：
4.8
通讯作者：
Lindholm, D
中科院分区：
文献类型：
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作者：
Bornhauser, BC;Olsson, PA;Lindholm, D
肌动蛋白细胞骨架和特定蛋白质之间的动态相互作用对细胞形状和运动性的改变至关重要。在这里，我们描述了一种新的蛋白质MSAP(MIR相互作用的皂苷样蛋白)，它是神经突起生长的正向调节因子。MSAP在包括脑在内的不同组织中都有表达，其表观分子量为21 kDa。MSAP与Ezrin-Radioxin-moesin(ERM)样的肌球蛋白调节轻链相互作用蛋白(MIR)相互作用，这两种蛋白共同定位于细胞系和原代神经元。MSAP的过表达促进了神经母细胞瘤和PC12细胞的轴突生长，而通过RNA沉默下调MSAP导致了轴突形成的抑制。MSAP对轴突生长的刺激作用被MIR的过度表达所抑制，从而导致肌球蛋白调节轻链(MRLC)水平下降。通过阻断蛋白酶体的活性和MSAP的过度表达，MIR对MRLC的这种减少被抑制，这表明这对蛋白质的稳定性有影响。有证据表明，MIR通过诱导其泛素化来降低MRLC。结果表明，MIR通过泛素化作用控制MRLC的水平，MSAP的存在抵消了MIR对MRLC的影响。MSAP可以稳定MRLC，从而增加轴突生长。
Dynamic interactions between the actin cytoskeleton and specific proteins are crucial for changes in cell shape and motility. Here we describe a novel protein MSAP (MIR-interacting saposin-like protein) that is a positive regulator of neurite outgrowth. MSAP is expressed in different tissues, including brain, and has an apparent molecular weight of 21 kDa. MSAP interacts with the ezrin-radixin-moesin (ERM)-like myosin regulatory light chain-interacting protein (MIR), and the two proteins are co-localized in cell lines and in primary neurons. Overexpression of MSAP enhances neurite outgrowth in neuroblastoma and PC12 cells, whereas downregulation of MSAP using RNA silencing led to inhibition of neurite formation. The stimulation of neurite outgrowth by MSAP was abrogated by the overexpression of MIR, which induced a decrease in the levels of myosin regulatory light chain (MRLC). This reduction in MRLC by MIR was inhibited by blocking the activity of proteasome and by overexpression of MSAP, suggesting an effect on protein stability. Evidence was obtained that MIR decreases MRLC by inducing its ubiquitination. The results show that the levels of MRLC are controlled by MIR via ubiquitination and that the effect of MIR on MRLC is counteracted in the presence of MSAP. MSAP can stabilize MRLC and thus bring about an increase in neurite outgrowth.