The F-BAR protein CIP4 inhibits neurite formation by producing lamellipodial protrusions.
The F-BAR protein CIP4 inhibits neurite formation by producing lamellipodial protrusions.
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DOI：
10.1016/j.cub.2012.01.038
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发表时间：
2012-03-20
期刊：
影响因子：
9.2
通讯作者：
Dent, Erik W.
中科院分区：
文献类型：
--
作者：
Saengsawang, Witchuda;Mitok, Kelly;Viesselmann, Chris;Pietila, Lauren;Lumbard, Derek C.;Corey, Seth J.;Dent, Erik W.
神经突的形成是神经元早期发育中的重要事件。然而，对神经元形成神经突的机制知之甚少。F-BAR蛋白在感知和诱导膜弯曲中起作用。Cdc 42相互作用蛋白4（CIP 4）是F-BAR家族的一员，调节多种细胞类型的内吞作用。然而，关于CIP 4如何在神经元中发挥作用的数据很少。在这里，我们表明，CIP 4通过抑制神经突的形成在神经元发育中起着新的作用。值得注意的是，CIP 4不是通过内吞作用发挥这种作用，而是通过产生片状脂质突起。在原代皮层神经元中，CIP 4特异性地集中在延伸的板状伪足和丝状伪足的尖端，而不是如在其他细胞类型中的内体。CIP 4的过表达导致细胞体周围的片状伪足突起，随后延迟神经突形成并扩大生长锥。这些作用取决于CIP 4的F-BAR和SH 3结构域及其多聚化能力。相反，来自CIP 4缺失小鼠的皮质神经元启动神经突的速度是对照组的两倍。这是第一项证明F-BAR蛋白在神经元与非神经元细胞中功能不同的研究，并诱导板状伪足突起而不是内陷或丝状伪足样结构。
Neurite formation is a seminal event in the early development of neurons. However, little is known about the mechanisms by which neurons form neurites. F-BAR proteins function in sensing and inducing membrane curvature. Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, regulates endocytosis in a variety of cell types. However, there is little data on how CIP4 functions in neurons. Here we show that CIP4 plays a novel role in neuronal development by inhibiting neurite formation. Remarkably, CIP4 exerts this effect not through endocytosis, but by producing lamellipodial protrusions. In primary cortical neurons CIP4 is concentrated specifically at the tips of extending lamellipodia and filopodia, instead of endosomes as in other cell types. Overexpression of CIP4 results in lamellipodial protrusions around the cell body, subsequently delaying neurite formation and enlarging growth cones. These effects depend on the F-BAR and SH3 domains of CIP4 and on its ability to multimerize. Conversely, cortical neurons from CIP4-null mice initiate neurites twice as fast as controls. This is the first study to demonstrate that an F-BAR protein functions differently in neuronal vs. non-neuronal cells and induces lamellipodial protrusions instead of invaginations or filopodia-like structures.
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DOI：
10.1126/science.1191710
发表时间：
2010-09-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lee K;Gallop JL;Rambani K;Kirschner MW
通讯作者：
Kirschner MW
DOI：
10.1523/jneurosci.4433-10.2011
发表时间：
2011-02-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Soderling SH
影响因子：
4.8
作者：
Bu, Wenyu;Chou, Ai Mei;Ahmed, Sohail
通讯作者：
Ahmed, Sohail
DOI：
10.1073/pnas.1002747107
发表时间：
2010-09-14
影响因子：
11.1
作者：
Koduru, Suresh;Kumar, Lalit;Geha, Raif S.
通讯作者：
Geha, Raif S.
影响因子：
11.8
作者：
Chuang, JZ;Yeh, TY;Sung, CH
通讯作者：
Sung, CH