Ectopic expression of LIM-nebulette (LASP2) reveals roles in cell migration and spreading.

Ectopic expression of LIM-nebulette (LASP2) reveals roles in cell migration and spreading.
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DOI:
10.1002/cm.20304
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发表时间:
2008-10
影响因子:
--
通讯作者:
Moncman, Carole L.
Moncman, Carole L.
中科院分区:
其他
文献类型:
--
作者:
Deng, Xiaodi A.;Norris, Andrea;Panaviene, Zivile;Moncman, Carole L.

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LIM-nebulette(LASP 2)是一种小的粘着斑蛋白,是肌动蛋白结合蛋白的星云蛋白家族的成员。这种最近鉴定的nebulette位点的剪接变体在神经元组织中广泛表达并高度富集。除了LIM-nebulette是一种粘着斑蛋白并与zyxin相互作用的事实外,对其功能一无所知。考虑到LIM-雾化器与LASP 1具有相同的模块化组织和重叠的组织分布,我们分析了LIM-雾化器与LASP 1的作用。我们发现,LIM-nebulette是一种动态的粘着斑蛋白,它增加了纤维连接蛋白包被表面上成纤维细胞的附着和扩散速率。此外,LIM-nebulette从非运动细胞中的皮质细胞骨架募集到受刺激细胞前缘的局灶性粘附。在HeLa和NIH 3 T3细胞的融合培养物中,LIM-nebulette与α-catenin共定位在假定的粘附连接中,而LASP 1没有这些区域。有趣的是,在PC6细胞中LIM-nebulette的过表达抑制了响应于生长因子的神经突生长。总的来说,我们的数据表明,LIM-nebulette和LASP 1在肌动蛋白细胞骨架中具有不同的作用。
LIM-nebulette (LASP2) is a small focal adhesion protein and a member of the nebulin family of actin binding proteins. This recently identified splice variant of the nebulette locus is widely expressed and highly enriched in neuronal tissue. Other than the facts that LIM-nebulette is a focal adhesion protein and interacts with zyxin, nothing is known about its function. Given that LIM-nebulette has an identical modular organization and overlapping tissue distributions to that of LASP1, we have analyzed the role of LIM-nebulette in comparison with that of LASP1. We find that LIM-nebulette is a dynamic focal adhesion protein that increases the rate of attachment and spreading of fibroblasts on fibronectin coated surfaces. Additionally, LIM-nebulette is recruited from the cortical cytoskeleton in non-motile cells to focal adhesions at the leading edge of stimulated cells. In confluent cultures of HeLa and NIH3T3 cells, LIM-nebulette co-localizes with α-catenin in putative adherens junctions, whereas LASP1 is devoid of these areas. Interestingly, overexpression of LIM-nebulette in PC6 cells inhibits neurite outgrowth in response to growth factors. Collectively, our data indicate that LIM-nebulette and LASP1 have distinct roles in the actin cytoskeleton.
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