A Cilia Independent Role of Ift88/Polaris during Cell Migration.
A Cilia Independent Role of Ift88/Polaris during Cell Migration.
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DOI：
10.1371/journal.pone.0140378
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kuehn EW
中科院分区：
文献类型：
--
作者：
Boehlke C;Janusch H;Hamann C;Powelske C;Mergen M;Herbst H;Kotsis F;Nitschke R;Kuehn EW
Ift 88是鞭毛内转运（Ift）复合物B的中心组分，对于从单细胞生物到哺乳动物的纤毛和鞭毛的构建是必需的。Ift 88的缺失导致纤毛的缺失，并导致左右不对称缺陷、Hedgehog信号传导紊乱和多囊肾病，所有这些都可以通过纤毛功能异常来解释。此外，已经描述了Ift 88的许多纤毛外功能，其影响细胞周期、有丝分裂和T细胞受体靶向免疫突触。类似地，另一种必需的纤毛分子，驱动蛋白-2亚基Kif 3a，其在纤毛中转运Ift-B，影响微管（MT）动力学在独立于纤毛的迁移细胞的前沿。我们现在表明，Ift 88的损失损害细胞迁移无关的纤毛。迁移MDCK细胞的极化需要Ift 88，Ift 88耗尽的细胞在前沿具有较少的MT。MT动力学和MT成核都不依赖于Ift 88。我们的研究结果分离的功能Ift 88从Kif 3a以外的纤毛，并建议一种新的纤毛外功能Ift 88。未来的研究需要解决Ift 88的不同纤毛外功能的统一机制。
Ift88 is a central component of the intraflagellar transport (Ift) complex B, essential for the building of cilia and flagella from single cell organisms to mammals. Loss of Ift88 results in the absence of cilia and causes left-right asymmetry defects, disordered Hedgehog signaling, and polycystic kidney disease, all of which are explained by aberrant ciliary function. In addition, a number of extraciliary functions of Ift88 have been described that affect the cell-cycle, mitosis, and targeting of the T-cell receptor to the immunological synapse. Similarly, another essential ciliary molecule, the kinesin-2 subunit Kif3a, which transports Ift-B in the cilium, affects microtubule (MT) dynamics at the leading edge of migrating cells independently of cilia. We now show that loss of Ift88 impairs cell migration irrespective of cilia. Ift88 is required for the polarization of migrating MDCK cells, and Ift88 depleted cells have fewer MTs at the leading edge. Neither MT dynamics nor MT nucleation are dependent on Ift88. Our findings dissociate the function of Ift88 from Kif3a outside the cilium and suggest a novel extraciliary function for Ift88. Future studies need to address what unifying mechanism underlies the different extraciliary functions of Ift88.