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Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation

机译:Fat2通过WAVE调节复合物来驱动组织旋转过程中的集体细胞迁移

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Directional cell movements during morphogenesis require the coordinated interplay between membrane receptors and the actin cytoskeleton. The WAVE regulatory complex (WRC) is a conserved actin regulator. Here, we found that the atypical cadherin Fat2 recruits the WRC to basal membranes of tricellular contacts where a new type of planar-polarized whip-like actin protrusion is formed. Loss of either Fat2 function or its interaction with the WRC disrupts tricellular protrusions and results in the formation of nonpolarized filopodia. We provide further evidence for a molecular network in which the receptor tyrosine phosphatase Dlar interacts with the WRC to couple the extracellular matrix, the membrane, and the actin cytoskeleton during egg elongation. Our data uncover a mechanism by which polarity information can be transduced from a membrane receptor to a key actin regulator to control collective follicle cell migration during egg elongation. 4D-live imaging of rotating MCF10A mammary acini further suggests an evolutionary conserved mechanism driving rotational motions in epithelial morphogenesis.
机译:形态发生过程中的定向细胞运动需要膜受体和肌动蛋白细胞骨架之间的协同相互作用。 WAVE调节复合物(WRC)是保守的肌动蛋白调节剂。在这里,我们发现非典型钙粘蛋白Fat2将WRC募集到三细胞接触的基膜,在那里形成了一种新型的平面极化鞭状肌动蛋白突起。 Fat2功能的丧失或其与WRC的相互作用会破坏三细胞突起,并导致形成非极性丝状伪足。我们提供了一个分子网络的进一步证据,在该网络中,受体酪氨酸磷酸酶Dlar与WRC相互作用,从而在卵伸长过程中偶联了细胞外基质,膜和肌动蛋白细胞骨架。我们的数据揭示了一种机制,通过该机制可以将极性信息从膜受体转导至关键的肌动蛋白调节剂,从而控制卵子伸长过程中集体卵泡细胞的迁移。旋转MCF10A乳腺腺泡的4D实时成像进一步表明,在上皮形态发生中驱动旋转运动的进化保守机制。

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