Filamins regulate cell spreading and initiation of cell migration.
Filamins regulate cell spreading and initiation of cell migration.
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DOI：
10.1371/journal.pone.0007830
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发表时间：
2009-11-13
期刊：
影响因子：
3.7
通讯作者：
Calderwood DA
中科院分区：
文献类型：
--
作者：
Baldassarre M;Razinia Z;Burande CF;Lamsoul I;Lutz PG;Calderwood DA
哺乳动物细丝蛋白(Flans)是一个由三个大的肌动蛋白结合蛋白组成的家族。该家族的创始成员Flna通过细胞生物学分析和在脑室周围异位的神经元迁移障碍中发现Flna突变而与迁移有关。然而，最近的基因敲除研究质疑了Flna与细胞迁移的相关性。在这里，我们使用shRNA介导的FLNA、FLNB或FLNA和FLNB的敲除，或者，或者，所有三个FLN的急性蛋白酶体降解，来产生FLN缺陷的细胞，并评估它们的迁移能力。我们报道，丢失Flna或FlnB对迁移几乎没有影响，但Flna和Flb的敲除，或所有三个Fln的蛋白分解，都会阻碍迁移。观察到的缺陷主要是运动启动的缺陷，而不是运动速度的维持问题。缺乏Fln的细胞在扩散过程中也会受到损害。重新表达全长的FLNA，但不重新表达缺失免疫球蛋白结构域19至21的突变的FLNA，既逆转了迁移的扩散，也逆转了对启动迁移的抑制。我们的结果确定了FLN在细胞迁移和扩散中的作用，并表明其他FLN的补偿可能掩盖了单个基因敲除或基因敲除细胞的表型。我们认为，FLN与跨膜或信号蛋白之间的相互作用，至少部分由免疫球蛋白结构域19至21介导，对于细胞扩散和启动迁移都是重要的。
Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration. Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration.
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影响因子：
12.4
作者：
通讯作者：
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影响因子：
11.4
作者：
Lad, Yatish;Kiema, Tiila;Ylaenne, Jari
通讯作者：
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影响因子：
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作者：
Jordan, M;Schallhorn, A;Wurm, FM
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影响因子：
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作者：
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通讯作者：
Walsh, CA
DOI：
10.1083/jcb.200707073
发表时间：
2007-12-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Stossel TP