Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation.
Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation.
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DOI：
10.1038/ncomms12603
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发表时间：
2016-08-22
影响因子：
16.6
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Liu Z;Ning G;Xu R;Cao Y;Meng A;Wang Q
微管通过促进内化受体的胞浆转运和Smad的核质穿梭，在转化生长因子-β信号转导中发挥作用。然而，对于这些过程是否需要肌动蛋白细丝，我们一无所知。在这里，我们报道了斑马鱼肌动蛋白捆绑蛋白fscn1a在中内胚层前体中的高表达，其表达受到转化生长因子-β超家族成员Nodal的直接调控。Fscn1a基因敲除或敲除导致斑马鱼胚胎结节信号转导和内胚层形成减少。Fscn1与转化生长因子-β家族的I型受体特异性地相互作用，它的缺失破坏了受体与肌动蛋白细丝之间的联系，并将内化的受体隔离到笼状蛋白包被的小泡中。因此，在斑马鱼内胚层形成过程中，Fscn1作为转化生长因子-β家族I型受体和肌动蛋白细丝之间的分子连接物，促进内化受体从包被分子筛蛋白的小泡向早期内吞体内转运。目前尚不清楚细胞骨架如何在受体下游协助转化生长因子-β信号传递。在斑马鱼中，作者证明了肌动蛋白捆绑蛋白FSCN1与转化生长因子-βI型受体ALK4和5相互作用，使肌动蛋白细丝介导的囊泡运输和内胚层形成。
Microtubules function in TGF-β signalling by facilitating the cytoplasmic trafficking of internalized receptors and the nucleocytoplasmic shuttling of Smads. However, nothing is known about whether actin filaments are required for these processes. Here we report that zebrafish actin-bundling protein fscn1a is highly expressed in mesendodermal precursors and its expression is directly regulated by the TGF-β superfamily member Nodal. Knockdown or knockout of fscn1a leads to a reduction of Nodal signal transduction and endoderm formation in zebrafish embryos. Fscn1 specifically interacts with TGF-β family type I receptors, and its depletion disrupts the association between receptors and actin filaments and sequesters the internalized receptors into clathrin-coated vesicles. Therefore, Fscn1 acts as a molecular linker between TGF-β family type I receptors and the actin filaments to promote the trafficking of internalized receptors from clathrin-coated vesicles to early endosomes during zebrafish endoderm formation. It is unclear how the cytoskeleton acts to assist in TGF-β signalling downstream of the receptor. Here, in zebrafish, the authors show that the actin-bundling protein FSCN1 interacts with TGF-β type I receptors ALK 4 and 5, enabling actin filament mediated vesicle trafficking and endoderm formation.