Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration.
Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration.
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DOI：
10.1186/1741-7007-9-54
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发表时间：
2011-08-11
期刊：
影响因子：
5.4
通讯作者：
Ridley AJ
中科院分区：
文献类型：
--
作者：
Bai SW;Herrera-Abreu MT;Rohn JL;Racine V;Tajadura V;Suryavanshi N;Bechtel S;Wiemann S;Baum B;Ridley AJ
细胞迁移在发育过程以及包括癌症在内的人类疾病进展中至关重要。大多数细胞迁移研究集中在迁移途径中已知的或预测的成分上。
在此，我们利用来自黑腹果蝇细胞全基因组RNA干扰形态学筛选的数据以及生物信息学，在人类细胞中鉴定出26种新的形态和细胞骨架组织调节因子。这些包括先前与从智力障碍、唐氏综合征和亨廷顿病到RNA和DNA结合基因等广泛功能相关的基因。我们根据表型将这些基因分为七组，并确定那些影响细胞迁移的基因。我们进一步对七个基因（FAM40A、FAM40B、ARC、FMNL3、FNBP3/FBP11、LIMD1和ZRANB1）的一个子集进行了表征，每个基因对细胞形状、肌动蛋白丝分布和细胞迁移都有不同的影响。有趣的是，在一些情况下，与单个果蝇同源物密切相关的同工型具有不同的表型。例如，FAM40B缺失导致细胞伸长和尾部回缩缺陷，而FAM40A缺失则减少细胞铺展。
我们的研究结果确定了多个在果蝇和人类之间高度保守的细胞迁移和细胞骨架信号调节因子，并表明密切相关的旁系同源物在这些过程中可能具有非常不同的功能。
Cell migration is essential during development and in human disease progression including cancer. Most cell migration studies concentrate on known or predicted components of migration pathways. Here we use data from a genome-wide RNAi morphology screen in Drosophila melanogaster cells together with bioinformatics to identify 26 new regulators of morphology and cytoskeletal organization in human cells. These include genes previously implicated in a wide range of functions, from mental retardation, Down syndrome and Huntington's disease to RNA and DNA-binding genes. We classify these genes into seven groups according to phenotype and identify those that affect cell migration. We further characterize a subset of seven genes, FAM40A, FAM40B, ARC, FMNL3, FNBP3/FBP11, LIMD1 and ZRANB1, each of which has a different effect on cell shape, actin filament distribution and cell migration. Interestingly, in several instances closely related isoforms with a single Drosophila homologue have distinct phenotypes. For example, FAM40B depletion induces cell elongation and tail retraction defects, whereas FAM40A depletion reduces cell spreading. Our results identify multiple regulators of cell migration and cytoskeletal signalling that are highly conserved between Drosophila and humans, and show that closely related paralogues can have very different functions in these processes.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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Rho GTPases控制细胞运动过程中的极性，突出和粘附。
影响因子：
7.8
作者：
Nobes, C D;Hall, A
通讯作者：
Hall, A
影响因子：
5.3
作者：
Kemp, HA;Sprague, GF
通讯作者：
Sprague, GF
影响因子：
16.2
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
11.4
作者：
Chan, DC;Bedford, MT;Leder, P
通讯作者：
Leder, P