The actin-binding protein UNC-115/abLIM controls formation of lamellipodia and filopodia and neuronal morphogenesis in Caenorhabditis elegans.
The actin-binding protein UNC-115/abLIM controls formation of lamellipodia and filopodia and neuronal morphogenesis in Caenorhabditis elegans.
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肌动蛋白结合蛋白 UNC-115/abLIM 控制线虫板状伪足和丝状伪足的形成以及神经元形态发生。
DOI：
10.1128/mcb.25.12.5158-5170.2005
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发表时间：
2005
影响因子：
5.3
通讯作者：
Lundquist,ErikA
中科院分区：
文献类型：
--
作者：
Yang,Yieyie;Lundquist,ErikA
肌动蛋白结合蛋白在发育和形态发生中的作用尚不清楚。肌动蛋白结合蛋白 UNC-115 与秀丽隐杆线虫寻路中 Rac 下游的细胞骨架信号传导有关，但 UNC-115 在此过程中的细胞作用仍不清楚。在此，我们报告 UNC-115 在 C 中的过度活跃。线虫神经元促进神经突、片状足和丝状足延伸的形成，与激活的 Rac 诱导的类似，通常在线虫中发现。线虫生长锥。我们表明，UNC-115 在神经元形态发生中的活性通过两种分子机制得到增强：当通过 c-Src 的肉豆蔻酰化序列异位驱动到质膜时，以及通过 UNC-115 肌动蛋白结合域中推定的丝氨酸磷酸化位点的突变。为了支持 UNC-115 调节肌动蛋白细胞骨架组织的假设，我们表明 UNC-115 在血清饥饿的 NIH 3T3 成纤维细胞中的活性导致板状伪足和丝状伪足的形成。我们得出的结论是，UNC-115 是神经元中板状伪足和丝状伪足形成的新型调节剂，可能在轴突寻路过程中位于生长锥中。
The roles of actin-binding proteins in development and morphogenesis are not well understood. The actin-binding protein UNC-115 has been implicated in cytoskeletal signaling downstream of Rac inCaenorhabditis elegansaxon pathfinding, but the cellular role of UNC-115 in this process remains undefined. Here we report that UNC-115 overactivity inC. elegansneurons promotes the formation of neurites and lamellipodial and filopodial extensions similar to those induced by activated Rac and normally found inC. elegansgrowth cones. We show that UNC-115 activity in neuronal morphogenesis is enhanced by two molecular mechanisms: when ectopically driven to the plasma membrane by the myristoylation sequence of c-Src, and by mutation of a putative serine phosphorylation site in the actin-binding domain of UNC-115. In support of the hypothesis that UNC-115 modulates actin cytoskeletal organization, we show that UNC-115 activity in serum-starved NIH 3T3 fibroblasts results in the formation of lamellipodia and filopodia. We conclude that UNC-115 is a novel regulator of the formation of lamellipodia and filopodia in neurons, possibly in the growth cone during axon pathfinding.